1. A comparative studies of the effects of Varidase and Urokinase on the experimental hyphema produced by the injection of rabbits auto-blood were performed in 20 eyes. 2. Subconjunctival injection of each enzymes were perfomed 1 hour after production of hyphema, and thereafter repeated once daily for 10 days. 3. Varidase increased the rate of absorption of hyphema, but Urokinase had no effect. 4. No side reactions were observed following the subconjunctival injection of these enzymes.
Absorption* ; Hyphema* ; Rabbits* ; Streptodornase and Streptokinase ; Urokinase-Type Plasminogen Activator

PURPOSE: Renal irradiation can lead to the development of radiation nephropathy, and this is characterized by the accumulation of extracellular matrix and final fibrosis. To determine the possible role of the glomerular epithelial cell, the radiation-induced changes in the expression of its genes associated with the extracellular matrix were analyzed. MATERIALS AND METHODS: Rat glomerular epithelial cells (GEpC) were irradiated with a single dose of 0, 2, 5, 10 and 20 Gy with using 6 MV LINAC (Siemens, USA), and the samples were collected 6, 24, 48 and 72 hours post-irradiation, respectively. Northern blotting, western blotting and zymography were used to measure the expression level of fibronectin (Fn), plasminogen activator inhibitor-1 (Pai-1), matrix metalloproteinases-2, 9 (MMP-2, 9), tissue inhibitor of metalloproteinase-2 (TIMP-2), tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA). RESULTS: Irradiation with a single dose of 10 Gy resulted in a significant increase in Fn mRNA since 24 hours post-irradiation, and a single dose of 5 and 10 Gy significantly increased the Fn immunoreactive protein measured 48 hours post-irradiation. An increase in Pai-1 mRNA and protein was also observed and especially, a single dose of 10 Gy significantly increased the mRNA measured 24 and 48 hours post-irradiation. The active MMP-2 measured 24 hours post-irradiation slightly increased in a dose dependent manner, but this increase did not reach statistical significance. The levels of MMP-9, TIMP-2, t-PA and u-PA appeared unaltered after irradiation. CONCLUSION: Irradiation of the glomerular epithelial cells altered the expression of genes associated with the extracellular matrix, implying that the glomerular epithelial cell may be involved in the development of radiation nephropathy.
Animals ; Blotting, Northern ; Blotting, Western ; Epithelial Cells* ; Extracellular Matrix ; Fibronectins* ; Fibrosis ; Plasminogen Activator Inhibitor 1* ; Plasminogen Activators ; Rats* ; RNA, Messenger ; Tissue Inhibitor of Metalloproteinase-2 ; Tissue Plasminogen Activator ; Urokinase-Type Plasminogen Activator

There is increasing evidence that thrombin is directly involved in the pathogenesis of cerebral edema after intracerebral hemorrhage. Some authors emphasize that early removal of hematoma using plasminogen activator can be an effective intervention that interrupts the cascade of events leading to increasing edema formation and white matter injury. Recently, there are many reports of the edema intensification following plasminogen activator-induced lysis of the intracerebral clot. The author reports a case who showed protracted perihematomal edema after hematoma evacuation and fibrinolysis therapy with urokinase. Considering that the benefit obtained from fibrinolysis therapy may be offset by an accentuation of its toxic edematous effect, further investigation into the use of urokinase for hematoma evacuation should be undertaken.
Brain Edema ; Cerebral Hemorrhage ; Edema* ; Fibrinolysis* ; Hematoma ; Plasminogen ; Plasminogen Activators ; Thrombin ; Urokinase-Type Plasminogen Activator*

BACKGROUND: There are evidences that uPA and its inhibitor play a key role in tumor spread. We studied whether uPA and PAI-1 expressions could serve as prognostic parameters along with clinical, gross and microscopic findings in gallbladder carcinomas. METHODS: We analyzed 42 cases of gallbladder carcinomas by immunohistochemical staining and clinicopathologic parameters. RESULTS: uPA and PAI-1 were more frequently expressed in the adenocarcinoma than in the normal or benign gallbladder tissue. The uPA expression in the glands of low grade adenocarcinoma was significantly correlated with both distant and lymph node metastases. The uPA expression in the stroma around the low grade adenocarcinoma was significantly correlated with either distant or lymph node metastasis. The PAI-1 expression was significantly correlated with lymph node metastasis only for both distant and lymph node metastases. In multivariate analysis, the lymphatic invasion was significantly related to poor survival (p= 0.0115). In univariate analysis, the cases without lymphatic invasion had prolonged survival. Positive expression of uPA in the glands of low-grade adenocarcinoma was significantly correlated with poor survival (p=0.0391). CONCLUSION: In conjunction with clinicopathologic findings, expressions of uPA and PAI-1 may be useful prognostic markers in gallbladder carcinomas.
Adenocarcinoma ; Gallbladder* ; Lymph Nodes ; Multivariate Analysis ; Neoplasm Metastasis ; Plasminogen Activator Inhibitor 1 ; Plasminogen Activators* ; Plasminogen* ; Prognosis ; Urokinase-Type Plasminogen Activator*

No abstract available.
Plasminogen Activators* ; Plasminogen*

OBJECTIVE: The most important biologic characters of malignant tumor are invasion and metastasis, and extracellular matrix is first barrier in metastatic process. Therefore, proteases are linked to the malignant phenotype of different solid tumor. METHODS: In this study, the expression of the matrix metalloproteinase (MMP)-2 and MMP-9 and of the serine protease urokinase-type plasminogen activator (uPA) and its inhibitor plasminogen activator inhibitor type 1 (PAI-1) in the ovarian epithelial tumors was investigated. Immunohistochemical expression of MMP-2, MMP-9, uPA, and PAI-1 were analyzed in formalin fixed tumor tissues of 20 benign cystadenomas, 20 low malignant potential (LMP) tumors, and 20 malignant ovarian cancer, including 10 FIGO stage I cancer and 10 stage III cancer. In the same tissue extracts, DNA levels of MMP-2, MMP-9, uPA, and PAI-1 were determined by PCR. RESULTS: The immunohistochemical expression and DNA level of MMP-2, MMP-9, uPA, and PAI-1 were low in benign ovarian tumors but significantly increased LMP tumors and malignant ovarian cancers. The highest values of all of the proteolytic enzymes were detected in stage III ovarian cancers with omentum metastases. There are significant correlations between expression of uPA and MMP. CONCLUSION: These results suggest that high expression of MMP-2, MMP-9, and uPA is associated with activity of tumor invasion and metastasis, and expressions of MMP-2 and MMP-9 are correlated with uPA activity.
Cystadenoma ; DNA ; Extracellular Matrix ; Female ; Formaldehyde ; Neoplasm Metastasis ; Omentum ; Ovarian Neoplasms ; Ovary* ; Peptide Hydrolases ; Phenotype ; Plasminogen Activator Inhibitor 1 ; Plasminogen Activators ; Polymerase Chain Reaction ; Serine Proteases ; Tissue Extracts ; Urokinase-Type Plasminogen Activator*

PURPOSE: We measured the gastric cancer tissue uPA and plasminogen activator inhibitor-1 (PAI-1) levels and compared them to those of the peripheral and portal blood levels to evaluate the correlation. MATERIALS AND METHODS: Tissue uPA and PAI-1 levels were measured by ELISA assay (Monozyme, Netherland) in paired 85 normal and cancer tissues resected from gastric cancer patients. In 50 patients, blood uPA and PAI-1 levels were measured from pre- operative peripheral and portal blood, post-operative portal blood. RESULTS: Gastric cancer tissue uPA and PAI-1 levels increased from the early stage. The elevated cancer-to-normal ratios of the uPA and PAI-1 were constant from stage I to IV. There were correlations of uPA between normal and cancer tissues (r2=0.38) and between peripheral and pre-resection portal blood level (r2=0.64). There were no correlations between tissue PAI-1 level and blood PAI-1 levels. However, there were correlations in PAI- 1/uPA ratio between cancer tissue and peripheral blood (r2=0.25), peripheral blood and pre- resection portal blood (r2=0.60). CONCLUSION: Even if the cancer tissue levels of uPA and PAI-1 increased from the early stage of gastric cancer, only blood uPA level correlated with tissue uPA level. A modest correlation found in PAI-1/uPA ratio between cancer tissue and blood suggests applicability of blood PAI-1/uPA ratio in predicting tissue uPA, PAI-1 expression.
Enzyme-Linked Immunosorbent Assay ; Humans ; Plasminogen Activator Inhibitor 1 ; Plasminogen Activators ; Stomach Neoplasms* ; Urokinase-Type Plasminogen Activator*

During angiogenesis, binding of urokinase plasminogen activator(uPA) and its receptor(uPAR) has been implicated as an important component of the angiogenesis pathway. We have produced a high-affinity competitive antagonist for the uPA receptor consisting of a fusion protein linking the endothelial growth factor(EGF)-like domain of uPA(residues 1-48) to the Fc domain of IgG. To determine whether this recombinant murine uPA1-48-IgG fusion protein could interfere with angiogenesis, we studied the effect of this compound on rat corneal angiogenesisinduced by basic fibroblast growth factor(bFGF). A hydrogel disk containing 250ng of bFGF and 4.2ug of uPA1-48-IgG fusiong protein in seven eyes, 250ug of bFGF and 4.2ug of phosphate-buffered saline(PBS) in another sseven eyes were implanted intrastromally 1.5mm from the superior limbus. At five days post-implantation of bFGF disk, the eyes treated with uPA1-48IgG fusion protein had reduced angiogenesis (mean score=3.1) compared with the PBS-treated controls(mean score=6.1)(P<0.05, Wilcoxon rank sum test). In a rat corneal pocket assay, murine uPA1-48-IgG fusion protein appears to inhibit bFGF-induced angiogenesis. Compounds that block uPAR binding of uPA may have therapeutic potential as anti-angiogenic agents.
Animals ; Corneal Neovascularization* ; Fibroblast Growth Factor 2* ; Fibroblasts ; Hydrogel ; Immunoglobulin G ; Plasminogen Activators* ; Plasminogen* ; Rats* ; Urokinase-Type Plasminogen Activator*

PURPOSE: Increased expression of the hepatocytes growth factor (HGF) receptor (c-Met) and urokinase type plasminogen activator (uPA) correlate with the development and metastasis of cancers. However, the mechanisms by which HGF/c-Met signaling mediate cancer progression and metastasis are unclear. Therefore, we investigated the roles of HGF/c-Met in tumor progression and metastasis in pancreatic cancer cell lines, L3.6PL and IMIN-PC2. MATERIALS AND METHODS: To see the functional c-Met protein, we were performed immunoprecipitation for functional c-Met protein. And also performed western bolot analysis and gel zymography for the functional uPA protein. To see the inhibition effects of uPAR monoclonal antibody on invasiveness of two pancreatic cancer cell lines, we were carried out standard two chamber invasion assay. RESULTS: At first, we observed the HGF-mediated c-Met phosphorylation and cell growth. c-Met phosphorylation was increased in the HGF-treated cells in a dose dependent manner. HGF resulted in increments of cell growth and ERK phosphorylation. HGF treatment increased the uPA expression and the uPA activity. A monoclonal antibody 3936, specific to uPAR receptor, inhibited HGF- mediated tumor cell invasion in a dose dependent manner. CONCLUSION: These results suggest that functional c- Met and HGF/c-Met signaling up-regulate the activity of uPA and result in increments of invasion-metastasis in the pancreatic cancer cells.
Cell Line ; Hepatocytes* ; Humans* ; Immunoprecipitation ; Neoplasm Metastasis ; Pancreatic Neoplasms* ; Phosphorylation ; Plasminogen Activators* ; Plasminogen* ; Receptors, Urokinase Plasminogen Activator ; Urokinase-Type Plasminogen Activator*

PURPOSE: We measured and compared the uPA, plasminogen activator inhibitor-1 (PAI-1) and uPA receptor (uPAR) levels in breast cancer tissues and blood of the patients to evaluate their clinical relevance for biotherapy. MATERIALS AND METHODS: uPA, PAI-1 (Monozyme, Netherland), uPAR (American Diagnostics, USA) levels were measured by ELISA assay in 192 breast cancer tissues, in 18 normal breast tissues and in 163 blood from breast cancer patients. RESULTS: There was a tendency of uPA increment from ductal carcinoma in situ while increment of PAI-1 and uPAR occurred from Ti. With the progression of cancer, uPA, PAI-1, uPAR tended to decrease; however, the uPA/uPAR, uPA/PAI-1 ratios remained unchanged. There was a correlation of uPA expression between normal and cancer tissues ( r(2)= 0.49). Correlation of uPA and PAI-1 was found in normal tissue and stage I cancer tissue while correlation of uPAR and PAI-1 was found with cancer progression. Between cancer tissue and blood significant correlations were found in uPA, PAI-1, uPAR levels. CONCLUSION: uPA, PAI-1, uPAR levels in cancer tissue elevated from the early stage maintaining correlative expressions with cancer progression. A positive correlation between cancer tissue and blood level suggested the applicability of the levels of uPA, PAI-1 or uPAR for detecting patients for biotherapy.
Biological Therapy* ; Breast Neoplasms* ; Breast* ; Carcinoma, Intraductal, Noninfiltrating ; Enzyme-Linked Immunosorbent Assay ; Humans ; Plasminogen Activator Inhibitor 1 ; Plasminogen Activators* ; Plasminogen* ; Urokinase-Type Plasminogen Activator*