1.Expression of Urokinase-type Plasminogen Activator (uPA) and Plasminogen Activator Inhibitor-1 (PAI-1) in Gallbladder Carcinoma.
Kee Hyung LEE ; Haeng Ji KANG ; Seung Yeoun LEE ; Moon Hyang PARK
Korean Journal of Pathology 2003;37(6):384-392
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*
3.Overexpression of Plasminogen Activator Inhibitor-1 in Advanced Gastric Cancer with Aggressive Lymph Node Metastasis.
Yun Suhk SUH ; Jieun YU ; Byung Chul KIM ; Boram CHOI ; Tae Su HAN ; Hye Seong AHN ; Seong Ho KONG ; Hyuk Joon LEE ; Woo Ho KIM ; Han Kwang YANG
Cancer Research and Treatment 2015;47(4):718-726
PURPOSE: The purpose of this study is to investigate differentially expressed genes using DNA microarray between advanced gastric cancer (AGC) with aggressive lymph node (LN) metastasis and that with a more advanced tumor stage but without LN metastasis. MATERIALS AND METHODS: Five sample pairs of gastric cancer tissue and normal gastric mucosa were taken from three patients with T3N3 stage (highN) and two with T4N0 stage (lowN). Data from triplicate DNA microarray experiments were analyzed, and candidate genes were identified using a volcano plot that showed > or = 2-fold differential expression and were significant by Welch's t test (p < 0.05) between highN and lowN. Those selected genes were validated independently by reverse-transcriptase-polymerase chain reaction (RT-PCR) using five AGC patients, and tissue-microarray (TMA) comprising 47 AGC patients. RESULTS: CFTR, LAMC2, SERPINE2, F2R, MMP7, FN1, TIMP1, plasminogen activator inhibitor-1 (PAI-1), ITGB8, SDS, and TMPRSS4 were commonly up-regulated over 2-fold in highN. REG3A, CD24, ITLN1, and WBP5 were commonly down-regulated over 2-fold in lowN. Among these genes, overexpression of PAI-1 was validated by RT-PCR, and TMA showed 16.7% (7/42) PAI-1 expression in T3N3, but none (0/5) in T4N0 (p=0.393). CONCLUSION: DNA microarray analysis and validation by RT-PCR and TMA showed that overexpression of PAI-1 is related to aggressive LN metastasis in AGC.
Gastric Mucosa
;
Humans
;
Lymph Nodes*
;
Neoplasm Metastasis*
;
Oligonucleotide Array Sequence Analysis
;
Plasminogen Activator Inhibitor 1
;
Plasminogen Activators*
;
Plasminogen*
;
Stomach Neoplasms*
4.Relationship between tissue plasminogen activator, plasminogen activator inhibitor and CT image in chronic subdural hematoma.
Dong Jun LIM ; Yong Gu CHUNG ; Youn Kwan PARK ; Jun Hyuk SONG ; Hoon Kap LEE ; Ki Chan LEE ; Jeong Wha CHU ; Yong Son YANG
Journal of Korean Medical Science 1995;10(5):373-378
The present study was performed to investigate the relationship between the concentrations of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI) and the CT images in 23 cases of chronic subdural hematomas (SDHs). The concentrations of t-PA and PAI-1 were quantified by enzyme-linked immunosorbent assay (ELISA). Chronic SDHs were divided into five groups according to their appearance on computed tomography: high-density (n = 4), isodensity (n = 8), low-density (n = 5), mixed-density (n = 3), layering (n = 3) types. The volume of hematoma was measured with an image analyzing software program. The concentrations of t-PA were higher in layering (41.2 +/- 0.3 ng/ml, mean +/- standard error of the mean) and high-density (40.0 +/- 1.1 ng/ml) types compared to those of low-density (23.3 +/- 4.1 ng/ml) and iso-density (25.1 +/- 3.7 ng/ml) types. The concentrations of PAI-1 were lower in layering (95.9 +/- 1.0 ng/ml) and high-density (103.4 +/- 34.5 ng/ml) types compared to that of low-density (192.5 +/- 2.6 ng/ml) type. So the ratio between t-PA and PAI-1 (t-PA/PAI) was greater in layering and high-density types. The volume of hematoma was larger in mixed-density and layering types but statistically insignificant. These results presumably suggest that the ratio between t-PA and PAI concentration may contribute to the pathogenesis of the chronic SDH.
Adult
;
Aged
;
Enzyme-Linked Immunosorbent Assay
;
Female
;
Hematoma, Subdural/*metabolism
;
Human
;
Male
;
Middle Age
;
Plasminogen Activator Inhibitor 1/*analysis
;
Tissue Plasminogen Activator/*analysis
;
Tomography, X-Ray Computed
5.Association between Plasma Levels of Plasminogen Activator Inhibitor-1 and Colorectal Neoplasms.
Eun Ran KIM ; Mun Hee YANG ; Yeun Jung LIM ; Jin Hee LEE ; Dong Kyung CHANG ; Young Ho KIM ; Hee Jung SON ; Jae J KIM ; Jong Chul RHEE ; Jin Yong KIM
Gut and Liver 2013;7(5):519-523
BACKGROUND/AIMS: Plasminogen activator inhibitor-1 (PAI-1) is important for tumor growth, Invasion, and metastasis. In this study, we investigated the relationship between plasma levels of PAI-1 and colorectal adenomas. METHODS: We reviewed the medical records of 3,136 subjects who underwent colonoscopy as a screening exam. The subjects were classified into a case group with adenomas (n=990) and a control group (n=2,146). Plasma PAI-1 levels were categorized into three groups based on tertile. RESULTS: The plasma levels of PAI-1 were significantly higher in adenoma cases than in controls (p=0.023). The prevalence of colorectal adenomas increased significantly with increasing levels of PAI-1 (p=0.038). In the adenoma group, advanced pathologic features, size, and number of adenomas did not differ among the three groups based on tertiles for plasma PAI-1 levels. Using multivariate analysis, we found that plasma level of PAI-1 was not associated with the risk of colorectal adenomas (p=0.675). Adjusted odds ratios for colorectal adenomas according to increasing plasma levels of PAI-1 were 0.980 (95% confidence interval [CI], 0.768 to 1.251) for the second-highest plasma level and 1.091 (95% CI, 0.898 to 1.326) for the highest level, compared with the lowest levels. CONCLUSIONS: These results suggest that elevated plasma PAI-1 levels are not associated with the risk of colorectal neoplasms.
Adenoma
;
Colonoscopy
;
Colorectal Neoplasms
;
Mass Screening
;
Medical Records
;
Multivariate Analysis
;
Neoplasm Metastasis
;
Odds Ratio
;
Plasma
;
Plasminogen
;
Plasminogen Activator Inhibitor 1
;
Plasminogen Activators
;
Prevalence
6.Coagulation and fibrinolytic activity in patients with acute cerebral infarction.
Feng LI ; Guibin ZHANG ; Wenzhou ZHAO
Chinese Medical Journal 2003;116(3):475-477
OBJECTIVETo measure the concentration of D-dimer (DD), tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1) and plasminogen (PLG) activity in plasma and cerebrospinal fluid in patients with acute cerebral infarction and to investigate their clinical significance.
METHODSThe concentrations of D-dimer, t-PA, and PAI-1 in plasma and cerebrospinal fluid in patients were measured by enzyme-linked immunosorbent assay (ELISA). The PLG biological activity was detected using the chromophore method. The results were compared with those of the controls.
RESULTSThe concentrations of D-dimer, t-PA and PAI-1 in cerebrospinal fluid and plasma in patients with acute cerebral infarction were much higher than those of normal subjects (P < 0.01). Conversely, the level of PLG activity was significantly lower in the patients than in the controls (P < 0.01).
CONCLUSIONHypercoagulability and secondary hyperfibrinolysis exist in patients with acute cerebral infarction.
Acute Disease ; Aged ; Blood Coagulation ; Cerebral Infarction ; blood ; Female ; Fibrin Fibrinogen Degradation Products ; analysis ; cerebrospinal fluid ; Fibrinolysis ; Humans ; Male ; Middle Aged ; Plasminogen ; analysis ; cerebrospinal fluid ; Plasminogen Activator Inhibitor 1 ; blood ; cerebrospinal fluid ; Tissue Plasminogen Activator ; blood ; cerebrospinal fluid
7.Effect of Cilazapril on endothelial cell function and fibrinolysis system in the canine atrial fibrillation models.
Wei-min LI ; Wei HAN ; Zi-jun LIANG ; Dong-lai WU ; Yong-lin HUANG ; Shang-jin CUI ; Yue LI
Chinese Journal of Cardiology 2005;33(5):469-472
OBJECTIVETo investigate the effect of cilazapril on endothelial cell function and fibrinolysis system in the canine atrial fibrillation (AF) models.
METHODSAll canines were divided into three groups: (1) Control group, without atrial pacing; (2) Atrial pacing group, in which atrial fibrillation was established by rapid atrial pacing at 400 bpm for 6 weeks; (3) Atrial pacing together with cilazapril group, in which cilazapril was given before and after atrial pacing. Nitric oxide (NO) of atrial endocardium was measured with NO-specific microelectrode. The expression of plasminogen activator inhibitor-1 (PAI-1) and tissue-type plasminogen activator (tPA) protein in atrium was determined by Western Blot analysis and immunohistochemical staining. Plasma levels of von Willebrand Factor (vWF), PAI-1 and tPA were analyzed by enzyme-linked immunoadsorbent assay.
RESULTSNO production from atrial endocardium was significantly increased in atrial pacing together with cilazapril group than atrial pacing group [(42.6 +/- 9.9) nmol/L vs (23.4 +/- 5.8) nmol/L, P < 0.05], whereas the plasma levels of vWF were decreased [(75.4 +/- 12.8)% vs (125.9 +/- 20.6)%, P < 0.05]. Compared to controls, the expression of atrium tPA protein in atrial pacing together with cilazapril group was significantly upregulated (4052 +/- 857 vs 1936 +/- 421, P < 0.05) and PAI-1 protein was downregulated (2487 +/- 542 vs 3164 +/- 827, P < 0.05). Cilazapril also significantly increased tPA antigen and decreased PAI-1 antigen in plasma.
CONCLUSIONCilazapril can favorably improve endothelial function and resume the balance of fibrinolysis system in AF, which might be of beneficial to hypercoagulated state in AF.
Angiotensin-Converting Enzyme Inhibitors ; pharmacology ; Animals ; Atrial Fibrillation ; blood ; drug therapy ; physiopathology ; Cilazapril ; pharmacology ; Disease Models, Animal ; Dogs ; Endothelial Cells ; drug effects ; physiology ; Female ; Fibrinolysis ; drug effects ; Immunohistochemistry ; Male ; Plasminogen Activator Inhibitor 1 ; analysis ; Tissue Plasminogen Activator ; analysis
8.Effects of simvastatin on cigarette smoke extract induced tissue-type plasminogen activator and plasminogen activator inhibitor-1 expression in human umbilical vein endothelial cells.
Xiao-yun HU ; Yu-hui MA ; Chen WANG ; Yuan-hua YANG
Chinese Medical Journal 2009;122(19):2380-2385
BACKGROUNDCigarette smoking has an influence on both arterial-type and venous-type thrombosis. However, little is known about the direct effect of cigarette smoke extract (CSE) on fibrinolytic activity of human umbilical vein endothelial cells (HUVECs). Most recently, simvastatin has been marked in its effect on endothelial cells protection and anticoagulation. In this study, the effect of CSE on the expression of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) in HUVECs was addressed. The role of simvastatin in CSE-induced fibrinolytic activity changes was investigated as well.
METHODSThe fourth to fifth generation of HUVECs were incubated respectively with 0, 5%, 10% and 20% CSE for 6 hours or exposed to 5% CSE for 0, 4, 6, 8, 12, 24 hours to determine the expression changes of t-PA and PAI-1 protein. Meanwhile, cells were also accordingly exposed either to 5% CSE alone or simvastatin pre-treated and 5% CSE for 24 hours to assess the role of simvastatin in CSE-induced t-PA and PAI-1 protein and mRNA expression in HUVECs. RT-PCR and ELISA techniques were used for detecting the t-PA or PAI-1 mRNA and protein.
RESULTSAfter 6-hour exposure to CSE, the expression levels of t-PA protein in 10% and 20% CSE-treated groups reduced significantly ((0.0365 +/- 0.0083) ng/ml, (0.0255 +/- 0.0087) ng/ml) when compared with that of control group ((0.0660 +/- 0.0120) ng/ml) (P < 0.05). In contrast, the levels of PAI-1 protein in 5%, 10% and 20% CSE-treated groups increased remarkably ((13.3225 +/- 0.5680) ng/ml, (14.2675 +/- 1.5380) ng/ml, (14.4292 +/- 1.6230) ng/ml) when compared with that of control group ((8.5193 +/- 0.7537) ng/ml) (P < 0.05). After stimulation with 5% CSE for 0, 4, 6, 8, 12, 24 hours, the levels of PAI-1 protein increased over time and reached the peak at 24 hours ((14.6400 +/- 1.0651) ng/ml), which was significantly higher than that of control group ((12.0656 +/- 0.6148) ng/ml) (P < 0.05). Additionally, CSE could up-regulate PAI-1 expression at both the mRNA and the protein levels. The levels of PAI-1 mRNA and protein increased significantly in 5% CSE-treated group ((8.8030 +/- 0.4745) ng/ml, (1.8155 +/- 0.0412) ng/ml) compared with those of control groups ((5.0588 +/- 0.2315) ng/ml, (1.3030 +/- 0.0647) ng/ml) (P < 0.01), and decreased after 2-hour simvastatin pre-treatment ((5.4875 +/- 0.3166) ng/ml, (1.3975 +/- 0.0297) ng/ml) (P < 0.01). No significant difference was found at the levels of t-PA protein and mRNA (P > 0.05).
CONCLUSIONSCSE inhibits the fibrinolytic activity of HUVECs in vitro. Simvastatin plays a protective role in CSE-induced fibrinolytic malfunction.
Cells, Cultured ; Endothelial Cells ; metabolism ; Fibrinolysis ; drug effects ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; pharmacology ; Plasminogen Activator Inhibitor 1 ; analysis ; biosynthesis ; genetics ; Simvastatin ; pharmacology ; Smoke ; adverse effects ; Tissue Plasminogen Activator ; analysis ; biosynthesis ; genetics ; Tobacco ; adverse effects ; Umbilical Veins ; cytology
9.Effects of cilazapril on endothelial cell function and fibrinolysis system in atrial fibrillation.
Wei HAN ; Wei-min LI ; Bao-dong XIE ; Yue LI ; Ji-yi ZHAO ; Yong-lin HUANG
Chinese Medical Journal 2005;118(12):1032-1035
Angiotensin-Converting Enzyme Inhibitors
;
pharmacology
;
Animals
;
Atrial Fibrillation
;
blood
;
drug therapy
;
physiopathology
;
Cilazapril
;
pharmacology
;
Dogs
;
Echocardiography
;
Endothelial Cells
;
drug effects
;
physiology
;
Fibrinolysis
;
drug effects
;
Nitric Oxide
;
biosynthesis
;
Plasminogen Activator Inhibitor 1
;
analysis
;
Tissue Plasminogen Activator
;
analysis
10.Tissue Plasminogen Activator and Plasminogen Activator Inhibitor-1 Levels in Patients with Acute Paraquat Intoxication.
Su Jin SEOK ; Su Ji KIM ; Hyo Wook GIL ; Jong Oh YANG ; Eun Young LEE ; Sae Yong HONG
Journal of Korean Medical Science 2011;26(4):474-481
To investigate the effects of reactive oxygen species (ROS) on tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) plasma levels, and their possible implications on clinical outcome, we measured tPA and PAI-1 levels in 101 patients with acute paraquat (PQ) intoxication. The control group consisted of patients who ingested non-PQ pesticides during the same period. tPA and PAI-1 levels were higher in the PQ group than in the controls. PQ levels were significantly correlated with ingested amount, timelag to hospital, tPA level, and hospitalization duration. tPA levels were correlated with PAI-1, fibrin degradation product (FDP), and D-dimer. D-dimer levels were lower in the PQ group than in the controls. Univariate analysis indicated the following significant determinants of death: age, ingested amount, PQ level, timelag to hospital, serum creatinine, lipase, pH, pCO2, HCO3-, WBC, FDP, PAI-1, and tPA. However, multivariate analysis indicated that only PQ level was significant independent factor predicting death. In conclusion, tPA and PAI-1 levels were higher, while D-dimer levels were lower in the PQ group than in the controls, implying that ROS stimulate tPA and PAI-1, but PAI-1 activity overrides tPA activity in this setting. Decreased fibrinolytic activity appears to be one of the clinical characteristics of acute PQ intoxication.
Acute Disease
;
Adult
;
Aged
;
Female
;
Fibrin Fibrinogen Degradation Products/analysis
;
Herbicides/blood/*poisoning
;
Humans
;
Male
;
Middle Aged
;
Paraquat/blood/*poisoning
;
Plasminogen Activator Inhibitor 1/*blood
;
Reactive Oxygen Species/metabolism
;
Risk Factors
;
Tissue Plasminogen Activator/*blood
;
Tomography, X-Ray Computed