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.
Female ; Glomerulonephritis, IGA/*enzymology ; Humans ; Male ; Plasminogen Activator Inhibitor 1/*analysis ; Podocytes/*enzymology ; Receptors, Urokinase Plasminogen Activator/*analysis ; Urokinase-Type Plasminogen Activator/*analysis

PURPOSE: The purposes of this study were to evaluate the efficacy of thrombolysis and to find optimal dose of urokinase and injection time by modified pulse-spray method with multiside-hole catheter in patients of arterriosclerosis obliterans of lower limbs. MATERIALS AND METHODS: Over a 2 month period, 5 cases of peripheral arterial occlusion of lower limbs were treated with 0.7--1.3 million unit of urokinase by modified pulse spray method. With antegrade puncture at the site of superficial femoral artery, the tip of modified pig tail catheter was initially placed approximately 2cm proximal to the distal end of the clot. The procedure started with the use of initial bolus dose of UK(100,000U) of lacing, and then small pulses of highly concentrated urokinase, which are forcefully sprayed throughout the thrombus at a rate of 20,000U/min. After the initial rapid period of deposition, the concentration of UK was reduced to 4,000U/min for residual thrombus. RESULTS: Complete clot lysis were achieved in 3 of 5 occlusions. Mean duration for completion of lysis was 140 min(40-180min) and initial recanalization of artery required 45min(20-90min). Total required dose of UK was 1,120,000U and mean dose for initial recanalization was 660,000U. No significant complications occurred except distal vasospasm in one case. CONCLUSION: Modified pulse spray method using ultrahigh and high dose urokinase is safe, reguires less time and has cost effectiveness in the management of peripheral arterial thrombolysis. Further study is warranted.
Arteries ; Catheters ; Cost-Benefit Analysis ; Femoral Artery ; Humans ; Lower Extremity ; Punctures ; Thrombosis ; Urokinase-Type Plasminogen Activator

PURPOSE: Cancer invasion is induced by several proteolytic enzyme systems associated with the destruction of basement membrane and extracellular matrix. Urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) have been reported as prognostic factors in breast cancer patients and plasminogen activation is regulated by various factor such as uPAR and growth factor. So we examined the tissue levels of urokinase-type plasminogen activator receptor (uPAR) in breast cancer patients. MATERIALS AND METHODS: Tissue uPAR levels were measured by ELISA assay in 268 breast cancer patients. RESULTS: The median and mean values of tissue uPAR level in breast cancer were 3.5 ng/mg and 4.8+-3.6 ng/mg cytosol protein, respectively. Tissue uPAR level was the highest in T1 stage, but there was no statistical significance between T stage (p >0.05). In nodal stage, there was also no difference in the value of uPAR according to progression. And the value of uPAR expression was not associated with estrogen and progesteron receptor status, number of involved node and percent of node involvement. In TNM stage, tissue uPAR levels were higher in patients with stage I-II than in patients with stage III-IV (p=0.027). In univariate analysis, nodal factor (p=0.0023) and TNM stage (p=0.0004) were significantly associated with overall survival. But, multivariate analysis showed that TNM stage was the only significant prognostic factor (p=0.0002). CONCLUSION: These results suggest that uPAR is mainly associated with initial tumor invasion and other factors might be involved in later stages of cancer progression.
Basement Membrane ; Breast Neoplasms* ; Breast* ; Cytosol ; Enzyme-Linked Immunosorbent Assay ; Estrogens ; Extracellular Matrix ; Humans ; Multivariate Analysis ; Plasminogen Activators* ; Plasminogen* ; Urokinase-Type Plasminogen Activator*

BACKGROUND/AIMS: The purpose of this study was to investigate the expression of urokinase-type plasminogen activator (uPA), uPA receptor (uPAR), and plasminogen activator inhibitor (PAI)-1 on podocytes in immunoglobulin A (IgA) glomerulonephritis (GN). METHODS: Renal biopsy specimens from 52 IgA GN patients were deparaffinized and subjected to immunohistochemical staining for uPA, PAI-1, and uPAR. The biopsies were classified into three groups according to the expression of uPA and uPAR on podocytes: uPA, uPAR, and a negative group. The prevalences of the variables of the Oxford classification for IgA GN were compared among the groups. RESULTS: On podocytes, uPA was positive in 11 cases and uPAR was positive in 38 cases; by contrast, PAI-1 was negative in all cases. Expression of both uPA and uPAR on podocytes was less frequently accompanied by tubulointerstitial fibrosis. CONCLUSIONS: Our results suggest a possible protective effect of podocyte uPA/uPAR expression against interstitial fibrosis.
Adolescent ; Adult ; Aged ; Atrophy ; Biological Markers/analysis ; Biopsy ; Female ; Fibrosis ; Glomerulonephritis, IGA/diagnosis/*enzymology/immunology ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Plasminogen Activator Inhibitor 1/*analysis ; Podocytes/*enzymology/immunology/pathology ; Receptors, Urokinase Plasminogen Activator/*analysis ; Urokinase-Type Plasminogen Activator/*analysis ; Young Adult

BACKGROUNDRecent studies have proved that brain-derived neurotrophic factor (BDNF) possesses angiogenic activity in vitro and in vivo. However, the proangiogenic mechanism of BDNF has not yet been provided with enough information. To explore the proangiogenic mechanism of BDNF, we investigated the effects of BDNF on extracellular proteolytic enzymes, including matrix metalloproteinases (MMPs) and serine proteases, particularly the urokinase-type plasminogen activator (uPA)-plasmin system in human umbilical vein endothelial cells (HUVECs) model.

METHODSTube formation assay was performed in vitro to evaluate the effects of BDNF on angiogenesis. The HUVECs were treated with various concentrations of BDNF (25 - 400 ng/ml) for different (6 - 48 hours), reverse transcriptase-polymerase chain reaction (RT-PCR) was used to assay MMP-2, MMP-9, TIMP-1, and TIMP-2 mRNA in HUVECs, and the conditioned medium was analyzed for MMP and uPA activity by gelatin zymography and fibrin zymography, respectively. uPA, plasminogen activator inhibitor (PAI)-1, tissue inhibitors of metalloproteinase (TIMP)-1, and TIMP-2 were quantified by western blotting analysis.

RESULTSBDNF elicited robust and elongated angiogeneis in two-dimensional cultures of HUVECs in comparison with control. The stimulation of serum-starved HUVECs with BDNF caused obvious increase in MMP-2 and MMP-9 mRNA expression and induced the pro-MMP-2 and pro-MMP-9 activation without significant differences in proliferation. However, BDNF had no effect on TIMP-1 and TIMP-2 production. BDNF increased uPA and PAI-1 production in a dose-dependent manner. Maximal activation of uPA and PAI-1 expression in HUVECs was induced by 100 ng/ml BDNF, while effects of 200 ng/ml and 400 ng/ml BDNF were slightly reduced in comparison with with those of 100 ng/ml. Protease activity for uPA was also increased by BDNF in a dose-dependent manner. BDNF also stimulated uPA and PAI-1 production beyond that in control cultures in a time-dependent manner from 12 hours to 48 hours after BDNF treatment.

CONCLUSIONSBDNF stimulates MMP and uPA/PAI-1 proteolytic network in HUVECs, which may be important to the acquisition of proangiogenic potential.

Brain-Derived Neurotrophic Factor ; pharmacology ; Cells, Cultured ; Gene Expression Regulation ; drug effects ; Humans ; Matrix Metalloproteinase 2 ; genetics ; Matrix Metalloproteinase 9 ; genetics ; Neovascularization, Physiologic ; drug effects ; Plasminogen Activator Inhibitor 1 ; genetics ; RNA, Messenger ; analysis ; Urokinase-Type Plasminogen Activator ; genetics

BACKGROUNDThe urokinase plasminogen activator system is believed to play an important role in degradation of the extracellular matrix associated with cartilage and bone destruction; however its precise roles in temporomandibular disorders have not yet been clarified. The aims of this study were to investigate the gene expression of fibrinolytic factors urokinase plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) in the articular cartilage of rabbit temporomandibular joint (TMJ) with disc displacement (DD) and to probe the relationship between fibrinolytic activity and cartilage remodeling.

METHODSDisc displacement of right joints was performed in 36 of 78 rabbits under investigation. The animals were sacrificed at 4 days and 1, 2, 4, 8 and 12 weeks after surgery, respectively. The right joints of these animals were harvested and processed for the examination of mRNA expression of uPA and PAI-1 in articular cartilage using in situ hybridization techniques.

RESULTSThe expression of uPA and PAI-1 was co-expressed weakly in the chondrocytes from transitive zone to hypertrophic zone and mineralized zone, while no hybridizing signals were shown in proliferative zone and superficial zone in control rabbits. The most striking was the up-regulation of uPA and PAI-1 mRNA in 4-day rabbits postoperatively at the onset of cartilage degeneration. The strongest hybridizing signals for uPA and PAI-1 were seen in 2-week rabbits postoperatively. After 2 weeks, the expression of uPA and PAI-1 began to decrease and reached nearly normal level at 12 weeks.

CONCLUSIONSThe expression of the uPA/PAI-1 system coincides with the pathological changes in condylar cartilage after DD. The uPA/PAI-1 system may be one of the essential mediators in articular cartilage remodeling.

Animals ; Cartilage, Articular ; metabolism ; Female ; Joint Dislocations ; metabolism ; pathology ; Male ; Mandibular Condyle ; metabolism ; pathology ; Plasminogen Activator Inhibitor 1 ; genetics ; RNA, Messenger ; analysis ; Rabbits ; Temporomandibular Joint ; metabolism ; Temporomandibular Joint Disc ; Urokinase-Type Plasminogen Activator ; genetics

BACKGROUND: Pleural effusion develops in approximately 40% of pneumonia patients. In 5-10% of these cases, it progresses to complicated parapneumonic effusion (CPPE) or empyema that requires drainage. The prognostic factors of CPPE and empyema remain to be clarified. We examined the treatment outcomes of CPPE and empyema and elucidating their prognostic factors. METHODS: One hundred and fifteen patients with CPPE or empyema, who were diagnosed and treated in Kyungpook National University Hospital (Daegu, Korea) between September 2001 and December 2005, were retrospectively analyzed. All the data was acquired from their chart review, and regarding treatment results, the time to defervescence and the length of hospital stay were analyzed. RESULTS: The treatment was successful in 101 patients with a success rate of 87.8%. Multivariate analysis showed the level of pleural fluid lactate dehydrogenase (LDH) to be a significant prognostic factor (odds ratio [OR] 7.37; 95% confidence interval [CI], 1.63 to 33.37; p=0.009). Pussy pleural fluid (r=0.236; p=0.01) and the frequency of urokinase use (r=0.257; p=0.01) correlated with the time to defervescence. However, there was no clinical factor that correlated with the length of hospital stay. CONCLUSION: The pleural fluid LDH level is a useful prognostic factor for monitoring treatment results of CPPE and empyema.
Drainage ; Empyema* ; Gyeongsangbuk-do ; Humans ; L-Lactate Dehydrogenase ; Length of Stay ; Multivariate Analysis ; Pleural Effusion ; Pneumonia ; Prognosis ; Retrospective Studies ; Urokinase-Type Plasminogen Activator

BACKGROUNDPulmonary embolism (PE) is a common and often fatal disease. Early after pulmonary thromboembolism, inflammation and associated intimal hyperplasia occur within the pulmonary arteries, similar to what is observed with chronic thromboembolic pulmonary hypertension. This study tested the hypothesis that thrombolytic and anticoagulant agents would have anti-inflammatory effects or inhibit intimal hyperplasia of involved pulmonary arteries.

METHODSSeventy-two male New Zealand white rabbits were randomly divided into two groups (54 rabbits in the PE group and 18 in the sham group). Experimental PE was induced in 54 rabbits by femoral vein injection of autologous blood clots and confirmed with pulmonary angiography, and other 18 rabbits underwent sham operations. Fifty-four rabbits in the PE group were randomly divided into three groups: a control group (treated with normal saline), a low-molecular- weight heparin (LMWH) group (treated with LMWH), and a urokinase (UK) group (treated with UK). Arterial blood gas was analyzed at 2, 7, and 28 days (n = 6 per time point by random group division), then lung tissues were removed and were analyzed for pro-inflammatory cytokines and chemokines, and were stained for intimal hyperplasia.

RESULTSThe overall survival of rabbits undergoing PE was 100%. PE distribution detected on digital signal angiography (DSA) and histopathology was shown in 67% of rabbits (36/54) in the bilateral low lobar pulmonary arteries (PAs). The results showed that alveolar-arterial partial pressure of oxygen (PO2) difference (PA-aO2) significantly increased and PO2 decreased in the control group compared with the sham group. Compared with controls, the UK group had a decreased level of PA-aO2 on day 2 (P < 0.05), however, there was no significant difference in the LMWH group. Compared with controls, the LMWH group had a decreased level of monocyte chemoattractant protein-1 (MCP-1) in affected tissue and serum samples on days 7 and 28 (P < 0.05), and the UK group had decreased levels on days 2 and 7 (P < 0.05). Compared with sham group, all PE groups had an increased level of interleukin-13 (IL-13) and transforming growth factor-β (TGF-β) in unaffected lung tissue samples at days 2 and 7. IL-13 in affected lung tissue in the LMWH group was decreased at all time points compared with controls (P < 0.05). However, TGF-β in affected lung tissue of the LMWH and UK groups increased at day 28. There was less intimal hyperplasia in involved pulmonary arteries at days 7 and 28 in the LMWH group compared with controls; there was no statistical difference in the UK group compared with controls.

CONCLUSIONSUK treatment can rapidly improve the V/Q mismatch in PE and appears a short-term anti-inflammatory benefit. However, LMWH maybe inhibit the later local inflammatory reaction and reduce intimal hyperplasia.

Animals ; Chemokines ; analysis ; Cytokines ; analysis ; Heparin, Low-Molecular-Weight ; therapeutic use ; Male ; Oxygen ; blood ; Pulmonary Artery ; drug effects ; pathology ; Pulmonary Embolism ; drug therapy ; immunology ; Rabbits ; Urokinase-Type Plasminogen Activator ; therapeutic use

OBJECTIVETo study the fibrinolytic activity in patients with acute promyelocytic leukemia (APL) and its alteration in all-trans retinoic acid (ATRA) and/or arsenic trioxide (ATO) treatment.

METHODSPlasma fibrinogen concentration was determined with the conventional method, and the levels of fibrin degradation products (FDP) and D-dimer were quantified with ELISA. Plasminogen was measured by chromogenic assay. Cell surface expression of Annexin II and u-PAR and their mRNA levels were measured by flow cytometry and real time-PCR, respectively.

RESULTSThe levels of FDP and D-dimer in APL were remarkably higher in APL patients than that in normal controls, while fibrinogen and plasminogen were lower. Both Annexin II and u-PAR were highly expressed on APL cells, which declined after treatment with ATRA and/or ATO, but remained higher than those on normal bone marrow mononuclear cells.

CONCLUSIONAbnormally high levels of Annexin II and u-PAR expression on APL cells may contribute to the increased production of plasmin, leading to primary hyperfibrinolysis in APL. ATRA and ATO therapy induces down-regulation of Annexin II and u-PAR expression, which may be contribute, at least in part, to the relief of the hemorrhagic complications in APL.

Adolescent ; Adult ; Aged ; Annexin A2 ; analysis ; Arsenicals ; therapeutic use ; Female ; Fibrinolysis ; Humans ; Leukemia, Promyelocytic, Acute ; drug therapy ; physiopathology ; Male ; Middle Aged ; Oxides ; therapeutic use ; RNA, Messenger ; genetics ; Tretinoin ; therapeutic use ; Urokinase-Type Plasminogen Activator ; analysis ; Young Adult