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)

UNC-45A is a molecular chaperone targeted to non-muscle myosins and is essential for cell division. Here, we show that UNC-45A mRNA and protein expression was elevated in human breast carcinomas and cell lines derived from breast carcinoma metastases. Moreover, small hairpin RNA knockdowns of endogenously overexpressed UNC-45A in the most metastatic cell line led to significant decreases in the rates of cell proliferation and invasion, concomitant with reduction in the interaction of myosin II with actin filaments. Exploring the mechanism of these findings further, we found that UNC-45A is alternatively expressed at the mRNA and protein levels as two isoforms. The two isoforms differ only by a proline-rich 15-amino-acid sequence near the amino-terminus. In the increased expression with metastatic activity, the ratio of the isoform mRNAs remained constant, but the 929-amino-acid protein isoform showed increases up to about 3-fold in comparison to the 944-amino-acid isoform. The differential accumulation was explained by cellular labeling experiments that showed that the 944 isoform is degraded at a 5-fold greater rate than the 929 isoform and that this degradation required the ubiquitin-proteasome system.
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PMID:Differential turnover of myosin chaperone UNC-45A isoforms increases in metastatic human breast cancer. 2180 25

Most cancer patients are treated with some combination of surgery, radiation, and chemotherapy. Despite recent advances in local therapy with curative intent, chemotherapeutic treatments for metastatic disease often remain unsatisfying due to severe side effects and incomplete long-term remission. Therefore, the evaluation of novel therapeutic options is of great interest. Conventional, along with newer treatment strategies target the immune system that suppresses genitourinary (GU) malignancies. Metastatic renal cell carcinoma and non-muscle-invasive bladder caner represent the most immune-responsive types of all human cancer. This review examines the rationale and emerging evidence supporting the anticancer activity of immunotherapy, against GU malignancies.
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PMID:Immunotherapy of genitourinary malignancies. 2248 27

A 66-year-old man with superficial bladder cancer was treated with transurethral resection (TURBT) in October 2011. The pathological diagnosis was urothelial carcinoma (UC), grade 2, T1. A second TURBT was performed one month later. The pathological diagnosis was UC, grade 3, T1. He was treated with intravesical bacillus Calmette-Guerin (BCG) after TURBT. His progress was satisfactory, but a small superficial bladder cancer was found on cystoscopy in August 2012. He was going to be treated with TURBT, but the serum alkaline phosphatase level was abnormally high on preoperative evaluation. Bone scintigraphy showed multiple bone metastases from non-muscle invasive bladder cancer (NMIBC) without local invasion. He was started on combined chemotherapy with 1,000 mg/m2 gemcitabine on days 1, 8 and 15 and 70 mg/m2 cisplatin on day 2 every four weeks. He received denosumab for multiple bone metastases at the same time. Although he subsequently developed severe hypocalcemia, treatment was continued, and he completed four courses of chemotherapy. Bone scintigraphy and contrast-enhanced computed tomography showed reduction of the multiple bone metastases, and alkaline phosphatase decreased to the normal range. It is rare for NMIBC without local invasion to metastasize to other organs. Thus, it is necessary to consider distant metastases in patients with NMIBC.
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PMID:[Non-muscle invasive bladder cancer with multiple bone metastasis without local invasion : a case report]. 2426 9

High-risk non-muscle invasive bladder cancer (NMIBC) progresses to metastatic disease in 10-15% of cases, suggesting that micrometastases may be present at first diagnosis. The prediction of risks of progression relies upon EORTC scoring systems, based on clinical and pathological parameters, which do not accurately identify which patients will progress. Aim of the study was to investigate whether the presence of CTC may improve prognostication in a large population of patients with Stage I bladder cancer who were all candidate to conservative surgery. A prospective single center trial was designed to correlate the presence of CTC to local recurrence and progression of disease in high-risk T1G3 bladder cancer. One hundred two patients were found eligible, all candidate to transurethral resection of the tumor followed by endovesical adjuvant immunotherapy with BCG. Median follow-up was 24.3 months (minimum-maximum: 4-36). The FDA-approved CellSearch System was used to enumerate CTC. Kaplan-Meier methods, log-rank test and multivariable Cox proportional hazard analysis was applied to establish the association of circulating tumor cells with time to first recurrence (TFR) and progression-free survival. CTC were detected in 20% of patients and predicted both decreased TFR (log-rank p < 0.001; multivariable adjusted hazard ratio [HR] 2.92 [95% confidence interval: 1.38-6.18], p = 0.005), and time to progression (log-rank p < 0.001; HR 7.17 [1.89-27.21], p = 0.004). The present findings provide evidence that CTC analyses can identify patients with Stage I bladder cancer who have already a systemic disease at diagnosis and might, therefore, potentially benefit from systemic treatment.
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PMID:Circulating tumor cells detection has independent prognostic impact in high-risk non-muscle invasive bladder cancer. 2459 51

In this study, we assessed the changes and prognostic relevance of syndecan-1 (SDC1) tissue and serum levels in bladder cancer (BC). SDC1 levels were analyzed in 213 samples (119 paraffin-embedded and 79 serum samples of BC patients and 15 controls) using immunohistochemistry and enzyme-linked immunosorbent assay. Results were correlated with clinicopathological characteristics and follow-up data, as well as previously determined serum levels of angiogenic factors (basic fibroblast growth factor, endostatin, angiostatin, angiopoietin, vascular endothelial growth factor, Tie2 and MMP-7). SDC1 staining was present in the cell membrane of normal bladder epithelium and non-muscle-invasive BC cells but was absent in a significant proportion of muscle-invasive carcinomas (P < .001). In contrast, stromal SDC1 expression was enhanced in muscle-invasive compared to non-muscle-invasive BCs (P = .001). Serum concentrations of the SDC1 ectodomain were higher in muscle-invasive BCs compared to controls or non-muscle-invasive carcinomas (P < .001 each). Lymph node-positive cases had the highest SDC1 serum concentrations (P < .001). SDC1 expression in stromal cells was independently associated with survival (hazard ratio = 2.034, 95% confidence interval 1.176-3.519, P = .011). SDC1 serum concentrations correlated with those of endostatin and matrix metalloproteinase 7. Loss of SDC1 in tumor cells and the parallel increase of serum SDC1 ectodomain concentration in high-stage, high-grade BCs suggest the involvement of SDC1 shedding in BC progression. In addition, high preoperative SDC1 serum levels may help to identify patients with lymph node metastases, supporting therapeutic decision-making. Presence of SDC1 in tumor stroma is an independent risk factor for patient survival and may therefore be used to select patients for more aggressive therapy.
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PMID:Enhanced stromal syndecan-1 expression is an independent risk factor for poor survival in bladder cancer. 2465 90

The goals of transurethral resection of bladder tumour (TURBT) for urothelial carcinoma are pathological staging and the removal of all visible tumour tissue. Typically, a deep and extensive resection beyond the basement membrane, including some muscularis propria, is performed. However, this also carries a risk of perforating the bladder wall, creating the ideal circumstances to facilitate peritoneal or abdominal metastases. Small, asymptomatic bladder perforations occur frequently and are associated with gender: female, decreasing body mass index, higher tumour stage, deeper infiltration and higher resection weight. Since many of these perforations are extraperitoneal, heal spontaneously and do not elicit any significant perioperative symptoms, they remain undiagnosed. Even in cases of intraperitoneal perforation, peritoneal tumour recurrence has been rarely reported. We report on the unusual case of a 61-year-old woman who underwent TURBT for non-muscle invasive urothelial carcinoma that was complicated by intraperitoneal bladder perforation requiring open repair.
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PMID:Tumour seeding as a result of intraperitoneal perforation during transurethral resection of non-muscle invasive bladder cancer. 2525 87

Urothelial carcinoma of the bladder comprises two long-recognized disease entities with distinct molecular features and clinical outcome. Low-grade non-muscle-invasive tumours recur frequently but rarely progress to muscle invasion, whereas muscle-invasive tumours are usually diagnosed de novo and frequently metastasize. Recent genome-wide expression and sequencing studies identify genes and pathways that are key drivers of urothelial cancer and reveal a more complex picture with multiple molecular subclasses that traverse conventional grade and stage groupings. This improved understanding of molecular features, disease pathogenesis and heterogeneity provides new opportunities for prognostic application, disease monitoring and personalized therapy.
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PMID:Molecular biology of bladder cancer: new insights into pathogenesis and clinical diversity. 2553 74

This study was carried out to clarify the presentation, treatment options, and prognosis of renal cell carcinoma (RCC) metastasis to the bladder in which we do not yet have a comprehensive understanding. A systematic Medline, Web of Science, Embase, Google, and Ichushi Web search was performed to identify articles describing RCC metastasis to the bladder. The final cohort included 65 patients. The majority (75%) experienced gross hematuria at the point of diagnosis of RCC. RCC metastasis to the bladder occurred both synchronously (23%) and metachronously (77%), and the median time for metachronous bladder metastasis following the diagnosis of RCC was 33 months. Of the 58 patients whose metastatic data were available, 36 (62%) had metastasis to the bladder only, while 22 (38%) had additional sites of metastasis. On pathology, clear cell carcinoma was the most common histology (92%) and all bladder tumors were consistent with RCC metastasis; the median tumor size was 2.1 cm, and two-thirds of cases were superficial (non-muscle invasive) disease. The 2-year cancer-specific survival rate in patients with solitary bladder metastasis was 71.1%, which was significantly higher than in patients with additional distant metastasis (25.8%, p = 0.007). Regarding the interval after the diagnosis of primary RCC, the 2-year cancer-specific survival rate in patients who experienced bladder metastasis after more than a 1 year follow-up was 58.4%, compared to 34.6% in their counterparts (p = 0.063). A curative resection may provide a good possibility of long-term survival, particularly in those with a solitary bladder metastasis and/or a long interval after nephrectomy.
Clin Exp Metastasis 2015 Feb
PMID:Bladder metastasis from renal cell carcinoma: retrospective analysis of 65 reported cases. 2563 Feb 70

Radical cystectomy (RC) with bilateral pelvic lymphadenectomy with or without perioperative chemotherapy is the golden standard treatment in muscle invasive and recurrent high-grade non-muscle invasive urothelial carcinoma of the bladder (UCB). Despite treatment with curative intent, up to 50% of patients develop metastasis and die from UCB due to micro-metastatic disease undetectable for current staging techniques prior to definitive therapy. Tumor cell dissemination is a crucial step in the natural history of the metastatic cascade. Circulating tumor cells (CTC) are malignant epithelial cells detectable in the peripheral blood of patients with various malignancies. In UCB, CTC are detectable in a significant number of patients prior to RC and associated with inferior outcomes. In this review, we summarize the current literature regarding CTC in UCB, discussing their potential on clinical decision-making regarding multimodal treatment and implications on the application of novel targeted therapies in the future. There is reliable evidence that presence of CTC in clinically non-metastatic UCB patients treated with RC are a powerful predictor for unfavorable outcomes and may be useful for adjuvant chemotherapy decision-making and monitoring. However, currently, the evidence is limited, and thus, integration of CTC in future UCB clinical trials is strongly recommended to shed more light on the potential of this promising biomarker.
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PMID:Do circulating tumor cells have a role in deciding on adjuvant chemotherapy after radical cystectomy? 2602 96

The management of bladder cancer, initially exclusively surgical, was recently improved by the development of chemotherapy. Chemotherapy can thus be proposed as bladder instillations in order to prevent recurrences of non-muscle-invasive cancer (NMIC), and systemically in case of muscle-invasive cancer (MIC). Chemotherapy can then be administered prior to surgery (neoadjuvant), as a complement to surgery (adjuvant), as an alternative to surgery as part of a multimodality treatment, and alone in palliative intent in case of metastatic cancer. Renal function and general health status of the patient help the decision-making and the choice of the chemotherapy regimen, which should be validated during a multidisciplinary meeting and presented to the patient during a dedicated medical and paramedical appointment.
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PMID:[The role of chemotherapy in bladder cancer]. 2620 98


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