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*

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*

OBJECTIVETo investigate the effect of anterior disc displacement on the expression of urokinase plasminogen activator and its inhibitor-1 (uPA/PAI-1) in synovial tissues.

METHODSForty Japanese white rabbits were used in this study. The animals were killed at 4 days, 1, 2, 4, 8 and 12 weeks postoperatively, respectively. In situ hybridization technology was applied to detect the expression of uPA/PAI-1 mRNA in synovial membrane.

RESULTSIn normal synovial tissues, synovial lining cells and a few fibrosblasts with mild positive staining were occasionally seen. More synovial lining cells and fibrosblasts with moderate postive signals were found 1 week after operation. Since then, the degree of staining for uPA/PAI-1 increased gradually. By the end of 12 weeks postoperatively, strong signals of uPA/PAI-1 mRNA were detected.

CONCLUSIONThere is a harmonized uPA/PAI-1 system existing in synovial tissues. The high expression of uPA and PAI-1 mRNA in synovial tissues indicates that the uPA/PAI-1 system may play an important role in the process of synovitis resulted from anterior disc displacement.

To examine the relationship between plasma plasminogen activator inhibitor-1[PAI-1]antigen concentration and diabetic retinopathy in non-insulin dependent diabetic patients, PAI-1 antigen levels and some fibri-nolytic parameters were studied in 89 non-insulin dependent diabetic patients[mean age 59.8 +/-11.3 years]and 25 normal adults as control[meanage 52.8 +/-14.7 years]. The diabetic patients were classified as three subgroups: no DR[n=34], NPDR[n=29]and PDR[n=26]according to the degree of retinopathy.The PAI-1 antigen concentration was measured by enzyme immunoassay[Innotest PAI Ag kit].The diabetic patients had a significantly higher mean PAI-1 antigen level [34.56 +/-17.80ng/milliliter ]compared to a control group[20.35 +/-15.78 ng/milliliter ][p<0.05].Plasma PAI-1 antigen level was significantly lower in diabetic patients with PDR[27.39 +/-15.54 ng/milliliter ]than in diabetics with no DR[36.87 +/-23.31 ng /milliliter ]or NPDR[39.43 +/-2 0.17 ng/milliliter ][p<0.05], probably because of more extensive systemic endothelial damage. These results support the hypothesis that impaired fibrinolysis due to elevated PAI-1 is associated with the development of retinopathy, and therefore the levels of PAI-1 can be used as useful indicator for the development and progression of proliferative retinopathy.
Adult ; Diabetes Mellitus, Type 2* ; Diabetic Retinopathy* ; Fibrinolysis ; Humans ; Plasma* ; Plasminogen Activator Inhibitor 1* ; Plasminogen Activators

OBJECTIVE: To evaluate the plasma concentration of plasminogen activator inhibitor 1, main regulator of fibrinolytic system in women with polycystic ovary syndrome and to clarify whether it may be involved in the pathogenesis of chronic anovulation. METHODS: Fibrinolytic system (plasma fibrinogen, plasminogen, plasminogen activator inhibitor 1 concentration) was assayed in women with polycystic ovary syndrome and compared to normal controls. RESULTS: Women with polycystic ovary syndrome had significantly higher plasminogen activator inhibitor 1 and fibrinogen concentration compared to normal controls. CONCLUSION: Women with polycystic ovary syndrome may have an imbalance in the fibrinolytic system that is tilted towards a reduced production of the proteolytic enzyme plasmin. It may result in impaired follicular rupture and anovulation at cellular level in the ovaries.
Anovulation ; Female ; Fibrinogen ; Fibrinolysin ; Humans ; Ovary ; Plasma ; Plasminogen ; Plasminogen Activator Inhibitor 1 ; Polycystic Ovary Syndrome* ; Rupture

No abstract available.
Female ; Glomerulonephritis, IGA/*enzymology ; Humans ; Male ; Plasminogen Activator Inhibitor 1/*analysis ; Podocytes/*enzymology ; Receptors, Urokinase Plasminogen Activator/*analysis ; Urokinase-Type Plasminogen Activator/*analysis

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*

BACKGROUND: Impaired fibrinolytic system has been considered to play an important role in the pathogenesis of coronary artery disease, especially associated with thrombus formation. To evaluate the pathogenetic role of fibrinolytic system in coronary artery disease, major determinants of fibrinolytic system, tissue plasminogen activator(t-PA) and palsminogen activator inhibitor-1(PAI-1) levels were measured in control(n=7) and chronic stable angina patients(n=7). METHODS: Blood samplings were done in resting state, venous occlusion and peak exercise. Levels of plasma t-PA antigen and PAI-1 antigen were measured by ELISA method. RESULTS: 1) In resting state, there was no significant difference in plasma level of t-PA(control group : 9.15+/-2.82ng/ml vs, study group ; 9.65+/-3.53ng/ml) and PAI-1(control group ; 20.27+/-9.98ng/ml vs, study group ; 17.43+/-3.53ng/ml) between each group. 2) With venous occlusion test, increment of plasma t-PA level was noted in both groups which was lower in patient group, however, this difference in increment was not statistically significant. 3) Increased plasma t-PA level was noted after exercise in both groups. 4) Plasma level of PAI-1 was not significantly changed after venous occlusion or exercise in both groups. CONCLUSIONS: In patients with chronic stable angina, there was no definite evidence of impaired fibriolytic system although plasma t-PA increased somewhat less after venous occlusion in patients with chronic stable angina than control.
Angina, Stable* ; Coronary Artery Disease ; Enzyme-Linked Immunosorbent Assay ; Humans ; Plasma* ; Plasminogen Activator Inhibitor 1 ; Plasminogen Activators* ; Plasminogen* ; Thrombosis ; Tissue Plasminogen Activator*

Tissue-type plasminogen activator (tPA) is a serine proteinase which plays important roles in functional and structural synaptic plasticity, neural migration, as well as excitotoxic injuries in several pathological situations including ischemic stroke, seizure and Alzheimer's disease (AD). It has been suggested that a divalent cation zinc also plays pathological roles in ischemia and seizure. Interestingly, it has been suggested that zinc and tPA may negatively regulate the activity or the level of each other by mechanism involving physical interaction between the two. In the present study, we investigated the effect of zinc in tPA activity and expression in rat primary astrocyte. Astrocytes were transiently exposed to 20~200micrometer Zn2+ for 2 h and then were recovered for 24 h. In the culture supernatants, zinc treatment concentration-dependently inhibited the activity of tPA which was determined by casein-plasminogen zymography. There was only marginal changes, if any, in the level of tPA mRNA and protein. On the other hand, the activity of an endogenous inhibitor of tPA, plasminogen activator inhibitor-1 (PAI-1) as well as its expression was increased by zinc treatment in a concentration-dependant manner. These results suggest that zinc-induced decrease in tPA activity was also, at least in part, regulated by indirect way by regulating the level of PAI-1. The decrease in tPA activity may be a part of body's plan to reduce excitotoxic neural injury in a condition of elevated zinc in the brain.
Alzheimer Disease ; Animals ; Astrocytes ; Brain ; Hand ; Ischemia ; Plasminogen ; Plasminogen Activator Inhibitor 1 ; Plasminogen Activators ; Plastics ; Rats ; RNA, Messenger ; Seizures ; Serine Proteases ; Stroke ; Tissue Plasminogen Activator ; Zinc

BACKGROUND: It is well known that coronary arterial thrombosis plays an important role in the pathogenesis of acute coronary syndrome and this has focused interest on the role of the fibrinolytic system, especially tissue plasminogen activator(t-PA) and plasminogen activator inhibitor-1(PAI-1), which are major determinants of fibrinolytic system. But there are considerable variations in the reported association between these two components and acute coronary syndrome. METHODS: To evaluate association between t-PA, PAI-1 and myocardial infarction, plasma level of t-PA and PAI-1 in resting state and after venous occlusion were measured and analysed in patients with previous myocardial infarction at least 6 months after the acute phase, who showed less than 70% luminal narrowing angiographically and control group. The relationship between t-PA, PAI-1 antigen and activity and relation to age, serum triglyceride, cholesterol, and peak creatine kinase(CK) enzyme were also analyzed. RESULTS: 1) In resting state, there was a significant difference of plasma level of both t-PA and PAI-1 antigen, activity between patient and control group(10.72+/-3.28 vs 8.16+/-4.03ng/ml, 0.53+/-0.34 vs 0.02+/-0.07U/ml, 26.24+/-8.30 vs 20.82+/-8.82ng/ml, 14.62+/-5.97 vs 6.99+/-6.44U/ml)(p<0.05), and resting plasma level of PAI-1 activity showed a good correlation with peak creatine kinase(CK) enzyme(r=0.76, p<0.01). 2) After venous occlusion, plasma level of t-PA antigen was significantly increased(8.16+/-4.03 vs 9.87+/-3.86ng/ml)(p<0.05) whereas t-PA activity and PAI-1 antigen were not significantly changed in control group. In patient group, t-PA antigen, t-PA activity and PAI-1 antigen were significantly inceased after venous occlusion(10.72+/-3.28 vs 14.66+/-5.41ng/ml, 0.53+/-0.34 vs 1.41+/-1.69U/ml, 26.24+/-8.30 vs 29.87+/-8.78ng/ml)(p<0.05). PAI-1 activity was significantly decreased after venous occlusion in both groups(6.99+/-6.44 vs 6.06+/-5.99U/ml, 14.62+/-5.97 vs 12.67+/-6.46U/ml)(p<0.05). CONCLUSION: Both fibrinolytic and anti-fibrinolytic systems are augmented in resting and after fibrinolysis stimulation test in patient group. These findings suggested a impairment of fibrinolytic system in patient group and a possibility that both elevated plasma levels of t-PA and PAI-1 may be markers of coronary artery disease.
Acute Coronary Syndrome ; Cholesterol ; Coronary Artery Disease ; Creatine ; Fibrinolysis ; Humans ; Myocardial Infarction* ; Phenobarbital ; Plasma* ; Plasminogen Activator Inhibitor 1 ; Plasminogen Activators* ; Plasminogen* ; Thrombosis ; Tissue Plasminogen Activator* ; Triglycerides