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

Head and neck cancer (HNSCC) is one of the most distressing human cancers, causing pain and affecting the basic survival functions of breathing and swallowing. Mortality rates have not changed despite recent advances in radiotherapy and surgical treatment. We have compared the expression of over 13,000 unique genes in 7 cases of matched HNSCC and normal oral mucosa. Of the 1,260 genes that showed statistically significant differences in expression between normal and tumor tissue at the mRNA level, the three top ranking of the top 5% were selected for further analysis by immunohistochemistry on paraffin sections, along with the tumor suppressor genes p16 and p53, in a total of 62 patients including 55 for whom >4-year clinical data was available. Using univariate and multivariate survival analysis, we identified SPARC/osteonectin as a powerful independent prognostic marker for short disease-free interval (DFI) (p < 0.002) and poor overall survival (OS) (p = 0.018) of HNSCC patients. In combination with other ECM proteins found in our analysis, PAI-1 and uPA, the association with DFI and OS became even more significant (p < 0.001). Our study represents the first instance of SPARC as an independent prognostic marker in HNSCC.
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PMID:Novel markers for poor prognosis in head and neck cancer. 1549 18

Tumor associated proteolysis is an essential mechanism in invasion and metastasis of cancer. The influence of the serine protease urokinase-like plasminogen activator (u-PA) and its inhibitor plasminogen activator inhibitor-1 (PAI-1) on the clinical prognosis of squamous carcinoma of the head and neck region (HNSCC) was evaluated. U-PA and PAI-1 levels were measured in tumor biopsies of 41 HNSCC patients and 6 biopsies of healthy oral mucosa using ELISA technique. Patients were followed for an average of 24 months. U-PA concentration in tumor tissue was four times higher than in healthy mucosa (4.96 ng/mg protein versus 1.32 ng/mg). PAI-1 levels were 22 times higher (69.55 ng/mg versus 3.18 ng/mg). Univariate Cox regression analysis revealed significant correlation (p=0.022) of PAI-1 with recurrence of the disease and no significance for u-PA. PAI-1 might become a new functional risk factor reflecting clinical prognosis.
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PMID:Urokinase-type plasminogen activator and its inhibitor plasminogen activator inhibitor-1. 2159 Jan 56

MiR-34a is a well-known tumor metastasis inhibitor, but only a few target genes involved in metastasis have been identified. In HNSCC, the role of miR-34a in metastasis has not been fully elaborated, and the target gene of miR-34a is still blind. Here we addressed that, the relative lower expression of miR-34a is associated with HNSCC lymphatic metastasis. HNSCC metastasis was found to be strongly suppressed in vitro and in vivo by over-expressing miR-34a. In order to screen the possible target genes of miR-34a in HNSCC, a microarray-based differential mRNA profiling mediated by miR-34a over-expression was performed, and AREG was identified as a pivotal target. We demonstrated that the mRNA and protein levels of AREG were greatly reduced when forcing miR-34a expression. The correlation between AREG mRNA levels and HNSCC metastatic phenotype was also significant in HNSCC tissues (p < 0.01). Moreover, the results of luciferase assay provided the further evidence that miR-34a degraded AREG mRNA through targeting the 3'-UTR site. Restoration of AREG expression partially rescued miR-34a-mediated cell invasion defects in vivo and in vitro. Additionally, Over-expressing miR-34a greatly reduced EGFR and uPA, which were reversed by re-expression of AREG. Taken together, these findings indicate that miR-34a targets AREG, and is essential in inhibition of HNSCC metastasis.
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PMID:MiR-34a suppresses amphiregulin and tumor metastatic potential of head and neck squamous cell carcinoma (HNSCC). 2576 34