Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.73 (urokinase-type plasminogen activator)
 10,685 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Despite the advances in the medical care of colorectal carcinoma patients, the prognosis has improved only marginally over recent decades. Thus, additional prognostic indicators would be of great clinical value to select patients for adjuvant therapy. In the present study, the antigen levels of urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1, and their immunohistochemical staining were compared in paired colorectal tumor (n = 64) and background colon tissue of the same patients with clinical and pathological staging. The antigen levels, measured with an ELISA method, were found to be significantly higher in cancer tissue (mean 1.92 ng/mg protein for uPA and 7.08 for PAI-1) than in corresponding normal mucosa (0.29 ng/mg protein for uPA and 1.11 ng/mg protein for PAI-1). There was a positive correlation between uPA and PAI-1 antigen levels and clinicopathological parameters such as grade (p < 0.001 and p = 0.01, respectively), while for Dukes' stage, only PAI-1 correlated positively (p = 0.018). Nodal status correlated positively with uPA but not with PAI-1 antigen levels. Immunohistochemical localization of both antigens was observed mainly in cancer cells and much less in stromal cells. Staining intensity increased from adenoma to adenocarcinoma. The degree of staining was associated with grade, Dukes' stage and nodal status for uPA (p < 0.001, p = 0.002, p < 0.001, respectively) and only with grade for PAI-1 (p = 0.007).
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PMID:Significance of urokinase-type plasminogen activator and plasminogen activator inhibitor-1 (PAI-1) expression in human colorectal carcinomas. 1221 97

Plasminogen activator inhibitor-1 (PAI-1) is a factor in urokinase-type plasminogen activator proteolytic system, which is important for tumour invasion and metastasis. Elevated PAI-1 levels in tumours are associated with poor prognosis. An insertion/deletion (4G/5G) promoter polymorphism in the PAI-1 gene affects activity of its product, the 4G/4G genotype being related to higher transcription levels. We assessed the association between the polymorphism and colorectal cancer risk in 206 cancer patients and 355 healthy controls. The results indicated that the PAI-1 gene polymorphism did not affect colorectal cancer risk. Nevertheless, within the case group, the 4G/4G genotype was associated with more advanced tumours (Dukes' C&D), whereas the 5G/5G homozygocity was associated with the Dukes' A&B tumours. The association with the 4G/4G presence was stronger in patients with proximal colon cancers (odds ratio= 6.02, 95% confidence interval, 1.15-31.54). Our results suggest that PAI-1 genotype may be a useful prognostic marker for colorectal cancer, however further specifically designed studies are needed to assess its value in this respect.
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PMID:Plasminogen activator inhibitor-1 gene polymorphism and colorectal cancer risk and prognosis. 1249 Mar 12

Soluble tetranectin (TN) was measured preoperatively in serum from 567 patients with primary colorectal cancer and levels were tested for association with prognosis. The prognostic significance of TN was also compared to that of plasminogen-activator inhibitor-1 (PAI-1), urokinase plasminogen activator (uPAR) and carcinoembryonic antigen (CEA). Significantly shorter survival was found for patients with TN levels below a cut-off point of 7.5 mg/l compared to patients with levels above, as illustrated by Kaplan-Meier curves. By Cox analyses, log TN, log soluble uPAR as well as log CEA were found to have an independent prognostic value for survival (log TN: HR = 0.47, 95% CI: 0.29-0.76); log soluble uPAR: HR = 1.65, 95% CI: 1.18-2.31; log CEA: HR = 1.I1, 95% CI: 1.03-1.20). Based on the multivariate model, a patient with a combination of low levels of TN and PAI-1 and elevated levels of soluble uPAR and CEA had a 2.43 increased risk as compared to a patient with median levels of these biochemical markers. Significant correlations were found with Dukes' stages for all the biochemical markers and between the respective biochemical markers. The findings confirm that TN is a strong prognostic factor in patients with colorectal cancer. TN may be valuable as a prognostic variable in future studies evaluating new treatment strategies for colorectal cancer.
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PMID:Serum tetranectin is an independent prognostic marker in colorectal cancer and weakly correlated with plasma suPAR, plasma PAI-1 and serum CEA. 1252 16

The aim of this study was to determine the expression of proteinases and inhibitors from the matrix metalloproteinase (MMP) (MMPs 1, 2, 3, 9, tissue inhibitors of metalloproteinases (TIMPs) 1, 2) and plasminogen activator ((PA) urokinase (uPA), tissue type (tPA), uPAR, plasminogen activator inhibitors (PAIs) 1, 2) systems in colorectal cancer pathology by gelatin zymography, enzyme-linked immunosorbent assays (ELISAs) and quenched fluorescent substrate hydrolysis. The levels of all studied MMPs, uPA, uPAR, TIMP-1 and PAIs were significantly greater in tumour tissues than normal tissues. However, tPA and TIMP-2 were greater in normal colon (P<0.05, Mann-Whitney) e.g. PAI-1: tumour, median 14.9 (range 0.2-80.2) ng/mg total protein; normal, 2.1 (0.1-65.0). Tumour levels of several factors, in particular MMP-1 and PAI-1, correlated with pathology, i.e. Dukes' stage, differentiation, lymphatic or vascular invasion and tumour depth. The interactions between proteinase systems in colorectal cancer are complex and the balance between active proteinases and their inhibitors is important for extracellular matrix (ECM) degradation/remodelling at each stage of the metastatic cascade.
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PMID:The plasminogen activator and matrix metalloproteinase systems in colorectal cancer: relationship to tumour pathology. 1270 68

The aim of this study was to investigate the relationship of Interleukin-8 (IL-8) with vascular endothelial growth factor (VEGF) and plasminogen activator system (PA system) in the progression of colorectal cancer (CRC). In eighty-seven patients with CRC, the levels of IL-8, and VEGF as representative angiogenic factors and urokinase-type plasminogen activator (uPA), uPA receptor (uPAR), plasminogen activator inhibitor-1 (PAI-1), and PAI-2 as representative invasive factors were quantitatively assayed in tumor and adjacent normal tissues. The levels of IL-8, VEGF, and PA system factors in tumor tissues were all significantly higher than those in normal tissues. The IL-8 level was significantly associated with tumor size, depth of infiltration, Dukes stage, and liver metastasis, and also significantly correlated with the levels of VEGF, uPAR, uPA, and PAI-1. The VEGF level was significantly associated with tumor size, vascular involvement. The levels of uPAR and PAI-1 were significantly associated with tumor size and depth of infiltration, and the uPAR level was associated with liver metastasis. The VEGF level was significantly correlated with the levels of uPAR and PAI-1. These results reveal that IL-8, VEGF, and PA system factors are contributed to tumor growth, invasion, and metastasis in CRC. Univariate analysis revealed that high levels of IL-8, VEGF, and uPAR were significantly associated with a shorter overall survival time; however, multivariate analysis identified only liver metastasis as an independent prognostic factor. In conclusion, IL-8 is responsible to tumor progression and liver metastasis of CRC, and the activation of PAS induced by IL-8 as well as VEGF may play an important role in the progression of CRC.
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PMID:Association of interleukin-8 and plasminogen activator system in the progression of colorectal cancer. 1608 82

To examine the relationship among the expression of urokinase-type plasminogen activator (u-PA), invasive/metastatic potential and prognosis of colorectal cancer (CRC), 58 patients with surgically resected advanced CRC were studied. u-PA expression and proliferating cell nuclear antigen labeling index (PCNA-LI) at the deepest invasive portion were examined immunohistochemically. u-PA expression was detected in 37 (63.8%) of 58 lesions. Lesions with liver metastasis showed a significantly (p < 0.01) higher incidence of u-PA expression than those without liver metastasis. Dukes staging also revealed a significant correlation with u-PA expression. The combination of u-PA expression and elevated PCNA-LI at the deepest invasive portion correlated significantly with prognosis. These results indicate that u-PA expression is an important predictor of CRC development and liver metastasis. Furthermore, combined analysis of u-PA expression and PCNA-LI at the deepest invasive portion is very useful in predicting CRC prognosis.
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PMID:Combined expression of urokinase-type plasminogen activator and proliferating cell nuclear antigen at the deepest invasive portion correlates with colorectal cancer prognosis. 2153 55


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