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Objective To fabricate iRGD targeted liposome-microbubble complex containing uPA ( iRGD-LMC) ,and to improve the thrombolytic efficiency and reduce the risk of thrombolysis by iRGD-LMC combining with ultrasound targeted microbubbles destruction ( UTMD ) to release drug into the thrombus site with the help of microbubble cavitation effect . Methods Biotinylated iRGD-MBs were fabricated by thin-film rehydration method .Biotinylated liposomes containing uPA were fabricated by freeze-thaw method and were conjugated to the biotinylated iRGD-MBs surface through biotin-avidin linkage . The iRGD-LMC was subjected to confocal microscopy to determine the particle morphology . The concentration , average diameter and size distribution were determined by particle sizing instrument . The uPA loading efficiency was measured by BCA Protein Assay Kit . Ultrasound imaging was performed using a Vevo 2100 ultrasound imaging system . The iRGD-LMC was irradiated by different ultrasound time and intensity to release drug . Thrombolytic effect in vitro of iRGD-LMC combined with UTMD was observed on the thrombosis model which was extracted from mouse blood . Results iRGD-LMC was successfully prepared . iRGD-LMC was exhibited a well-defined spherical morphology and homogeneous distribution ,like ordinary microbubbles . The concentration of iRGD-LMC was ( 0 .51 ± 0 .03 ) × 109 / ml and average diameter was ( 2 .62 ± 0 .12) μm . Drugs loading efficiency was ( 3878 .5 ± 97 .8) μg uPA per 108 microbubbles . iRGD-LMC could achieve contrast-enhanced ultrasound imaging in vitro . The thrombolytic effect of iRGD-LMC +US group ( 87 .66 ± 1 .69) ％ was the best in vitro ,and had significant difference with others groups ( P <0 .05) ,followed by iRGD-LMC group ( 53 .32 ± 4 .86) ％ and uPA group ( 51 .09 ± 9 .01) ％ ,Compared with PBS group ,US group ( 23 .56 ± 9 .46) ％ had thrombolytic effect . Conclusions iRGD-LMC is successfully prepared ,which has the advantages of high drug loading of liposomes and good acoustic properties of microbubbles . iRGD-LMC combined with UTMD achieves a significant thrombolytic effect in vitro .
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Objective To observe the clinical effect of intravenous thrombolytic therapy for central retinal artery occlusion (CRAO) with poor effect after the treatment of arterial thrombolytic therapy.Methods Twenty-four CRAO patients (24 eyes) with poor effect after the treatment of arterial thrombolytic therapy were enrolled in this study.There were 11 males and 13 females.The age was ranged from 35 to 80 years,with the mean age of (56.7± 15.6) years.There were 11 right eyes and 13 left eyes.The visual acuity was tested by standard visual acuity chart.The arm-retinal circulation time (A-Rct) and the filling time of retinal artery and its branches (FT) were detected by fluorescein fundus angiography (FFA).The visual acuity was ranged from light sensation to 0.5,with the average of 0.04±0.012.The A-Rct was ranged from 18.0 s to 35.0 s,with the mean of (29.7±5.8) s.The FT was ranged from 4.0 s to 16.0 s,with the mean of (12.9±2.3) s.All patients were treated with urokinase intravenous thrombolytic therapy.The dosage ofurokinase was 3000 U/kg,2 times/d,adding 250 ml of 0.9％ sodium chloride intravenous drip,2 times between 8-10 h,and continuous treatment of FFA after 5 days.Comparative analysis was performed on the visual acuity of the patients before and after treatment,and the changes of A-Rct and FT.Results After intravenous thrombolytic therapy,the A-Rct was ranged from 16.0 s to 34.0 s,with the mean of (22.4 ±5.5) s.Among 24 eyes,the A-Rct was 27.0-34.0 s in 4 eyes (16.67％),18.0-26.0 s in 11 eyes (45.83％);16.0-17.0 s in 9 eyes (37.50％).The FT was ranged from 2.4 s to 16.0 s,with the mean of (7.4± 2.6) s.Compared with before intravenous thrombolytic therapy,the A-Rct was shortened by 7.3 s and the FT was shortened by 5.5 s with the significant differences （x2=24.6,24.9;P＜0.01).After intravenous thrombolytic therapy,the visual acuity was ranged from light sensation to 0.6,with the average of 0.08 ± 0.011.There were 1 eye with vision of light perception (4.17％),8 eyes with hand movement/20 cm (33.33％),11 eyes with 0.02-0.05 (45.83％),2 eyes with 0.1-0.2 (8.33％),1 eye with 0.5 (4.17％) and 1 eye with 0.6 (4.17％).The visual acuity was improved in 19 eyes (79.17％).The difference of visual acuity before and after intravenous thrombolytic therapy was significant (x2=7.99,P＜0.05).There was no local and systemic adverse effects during and after treatment.Conclusion Intravenous thrombolytic therapy for CRAO with poor effect after the treatment of arterial thrombolytic therapy can further improve the circulation of retinal artery and visual acuity.
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Purpose To observe the thrombolytic effect of different ultrasonic frequencies combined with urokinase-containing targeted microbubble contrast agent on rabbit femoral artery,to explore the main influencing factors,and to determine the potential indicators related to recurrent embolism in the microcirculation.Materials and Methods Unilateral femoral arterial thrombosis models were established in the selected 72 New Zealand white rabbits,which were randomly divided into 12 groups,6 rabbits in each group.This study was performed on an experimental combination of three factors and different levels,including different ultrasonic frequencies (1.6,2.2,2.8 MHz),different ultrasonic irradiation time (30 and 60 min),and different urokinase dose (3 and 6 mg).Thrombolysis with urokinase-containing targeted microbubble was performed under low frequency ultrasonic assisted irradiation,the recanalization status of blood vessels was observed,and recurrent embolism in the microcirculation was confirmed by HE staining.Furthermore,rabbit blood samples were collected,with indicators,including 6-keto-prostaglandin F1a (6-keto-PGF1a),Thromboxane B2 (TXB2),P/T ratio (6-keto-PGF1a/TXB2) and P-selectin (SP) being detected.Results All the vessels were recanalized.There was no occurrence of recurrent embolism in the group with ultrasonic frequency of 2.2 MHz,radiation time of 30 min,and urokinase dose of 3 mg.Rabbits' blood vessels were observed to be not completely recanalized in other groups,accompanied with different degree of recurrent embolism in the microcirculation.6-keto-PGF 1 a content of the rabbits in the group without recurrent embolism obviously increased after thrombolysis,and the difference was statistically significant (P＜0.05).While,there was no statistical difference in other indicators (P＞0.05).Conclsion The thrombolysis with ultrasound frequency of 2.2 MHz,irradiation time of 30 min,and urokinase dose of 3 mg could achieve complete recanalization of blood vessels.Under the certain conditions of ultrasonic frequency,irradiation time and urokinase dosage,thrombus can be effectively dissolved.However,there may be risk of recurrent embolism in the microcirculation during thrombolysis process.The increase of 6-keto-PGF 1a content has a certain effect on reducing the formation of recurrent embolism in the microcirculation.
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Objective To investigate the significance and expression of uPA in the endometriosis .Methods Expressions of uPA in 30 cases of normal endometrium ,35 cases of eutopic endometrium were detected by the immunohistochemical SP and RT‐PCR methods .Results First ,in three groups ,the expression of uPA protein was mainly in the cytoplasm of endometrial glandular epithelial cells and stromal cells ,few was expressed in vascular endothelial cells ,which the expression of uPA protein in ectopic en‐dometrium of EMs was higher than eutopic and normal endometrium ,with significantly differences among 3 groups(P 0 .05) . Third ,the relative expression of uPA mRNA in ectopic endometrium of EMs was higher than eutopic and normal endometrium ,with a significant difference among 3 groups(P< 0 .05) .Conclusion uPA may play an important role in the pathogenisis of EMs .
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Objective To compare the curative effect and safety of salvia miltiorrhiza salt combined with urokinase and sim‐ple application of urokinase in the treatment of angina pectoris after thrombolysis of acute ST‐elevation myocardial infarction .Meth‐ods Totally 124 cases patients were random divided into treatment group and control group ,62 cases in each group ,two group were given coronary heart disease Ⅱ level prevention treatment and dissolved tied treatment (urine kinase 1 .5 million U dissolved Yu saline 100 mL in the 30 minutes within drops finished ,only with a times) ,then control group was given polarization liquid treat‐ment ,treatment group was given Salvia more phenol acid salt 200 mg diluted Yu 5% glucose or saline 250 mL in the vein drops note 15 days ,incidence of myocardial infarction and angina pectoris and drug side effects were observed .Results Incidence of angina pectoris was 25 .81% in the treatment group and control group was 56 .45% ,there were significant differences in the two groups (P<0 .05) .Conclusion Application of phenolic acids from salvia miltiorrhiza salt combined with urokinase in the treatment of a‐cute ST‐elevation myocardial infarction ,myocardial infarction and angina pectoris can be significantly reduced ,and with good clinical efficacy and fewer side effects ,and it is safety .
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Hypertensive intracranial hemorrhage (HICH) has high incidence and mortality, causing great economic and health burden. However, HICH is the only subgroup of stroke that has no clear treatment standard. Though traditional craniotomy still enjoys popularity in treating HICH, yet no clear clinical evidence support its benefit to neuronal function and prognosis. Recently minimally invasive surgery (MIS) begin to show great advantage to treat HICH. This review presented the current situation and recent progress of common MIS procedures for HICH, including stereotactic aspiration, neuroendoscopic evacuation and fibrinolysis treatment.
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Objective To compare the clinical effect of UK and rt-PA intravenous thrombolytic therapy for acute myocardial infarction.Methods By SAS statistical analysis system,72 patients with acute myocardial infarction were randomly divided into rt-PA group and UK group,each group had 36 cases.The coronary artery recanalization rate,bleeding events,adverse cardiovascular events,mortality,and cardiac troponin T(cTnT) level were recorded.Results In rt-PA group,0.5h,1 h,2h after the start of thrombolytic therapy,the coronary artery recanalization rate was significantly higher than that in the control group,the difference was statistically significant (x2 =7.32,6.12,5.81,all P ＜ 0.05).In rt-PA group,3 cases had bleeding events,2 cases died,and in UK group,5 cases had bleeding events,3 cases died,,there was no statistically significant difference between the two groups (x2 =1.22,P ＞ 0.05).In rt-PA group,there were 6 cases with adverse cardiovascular events,14 cases in the control group,the difference was statistically significant (x2 =4.56,P＜0.05).2 cases died in rt-PA group,3 cases died in UK group,the mortality between the two groups had no statistically significant difference (P ＞ 0.05).The cTnT level in the hospital 6h,12h was significantly higher than admission in two groups (t =6.67,6.30,4.11,4.22,4.40,all P ＜ 0.05).In rt-PA group,cTnT level in the hospital 6h,12h was significantly lower than that in UK group (t =5.92,6.61,all P ＜0.05).Conclusion Compared with UK,rt-PA in the treatment of acute myocardial infarction can increase recanalization rate,decrease adverse events and myocardial injury,it is worthy of clinical application.
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Objective To investigate the effect of intravenous thrombolytic therapy with urokinase on the neurological function and the concentration of serum matrix metalloproteinase 9 (MMP-9) in the patients with acute cerebral infarction.Methods The patients with acute cerebral infarction were divided into the experimental and control groups.The experimental group included 27 patients who were complied with thrombolytic criterion within 4.5 hours after stroke and were firstly treated by intravenous thrombolytic therapy with urokinase by 100 million units after 24 h and 300 mg aspirin by oral.The control group included 27 cases that were directly administrated by 300 mg aspirin 4.5 hours later after stroke.After 24 h,the two groups were administrated with other same conventional treatments such as neurotrophy,improvement of microcirculation,and control of blood-fat.The neurological function and dynamic concentration of serum MMP-9 were observed before treatment and after treatment.Results After treatment,the neurological deficit evaluation score in both groups was gradually reduced with the treatment time,and the neurological deficit evaluation score in the experimental group was significantly lower than that in the control group at the 1 st,3rd,and 14th day,respectively[(10.97 ± 1.53) Score vs (15.67 ±1.78)Score,t =8.35,P =0.03;(8.15 ± 1.40) Score vs(12.72 ± 3.31) Score,t =6.62,P =0.03; (5.87 ± 1.03) Score vs (11.92 ±2.05) Score,t =13.70,P =0.01].After treatment,the concentration of serum MMP-9 in both groups was reduced with the treatment time,and serum MMP-9 in the experimental group was significantly lower than that in the control group at the 1st,3rd,and 14th day,respectively[(282.84 ±37.51) ng/ml vs (316.90±36.75)ng/ml,t =3.37,P =0.00;(309.11±37.71)ng/mlvs (348.39 ±15.26) ng/ml,t =5.02,P=0.04;(264.68±31.91)ng/ml vs (302.81 ±36.30)ng/ml,t =4.10,P =0.03].Conclusions Intravenous thrombolytic therapy with urokinase can effectively reduce the neurological deficit and the produce of MMP-9 in patients with acute cerebral infarction.
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Objective: To investigate the expressions of uPA (urokinase-type plasminogen activator) and PAI-1 (plasminogen activator inhibitor-1) in human breast cancer tissues and their clinical significance. Methods: The expressions of uPA and PAI-1 in breast cancer tissue samples from 252 patients with breast cancer were detected by immunohistochemistry. The associations between the expressions of uPA and PAI-1 with the clinicopathological factors were evaluated by using Kruskal-Wallis rank sum test. The correlation of uPA expression and PAI-1 expression was examined by using Spearman's rank correlation test. The survival analysis was conducted to assess the impacts of uPA and PAI-1 expressions on the prognosis of patients with breast cancer. Results: The expressions of uPA and PAI-1 were related to nuclear grade, tumor size, axillary lymph node status and Ki67 expression (P < 0.05), and the expression of uPA was also related to HER-2 (human epidermal growth factor receptor 2) expression (P < 0.05). In breast cancer tissues, the expressions of uPA and PAI-1 showed a positive relationship (rs = 0.773, P = 0.000). In subgroups of patients with lymph node-negative and lymph node-positive breast cancer, a positive relationship (rs = 0.760, P = 0.000; rs = 0.780, P = 0.000) was also seen between uPA and PAI-1 expressions. The tumor size (P = 0.023), nuclear grade (P = 0.008), axillary lymph node status (P = 0.000) and the expressions of HER-2 (P = 0.033), uPA (P = 0.005) and PAI-1 (P = 0.023) were associated with DFS (disease-free survival). Of these factors, axillary lymph node status was an independent prognostic factor for patients with breast cancer. The result of subgroup analysis revealed that the expressions of uPA and PAI-1 could influence the DFS of patients with lymph node-negative breast cancer (P = 0.000; P = 0.045). Conclusion: The results of this study suggest that uPA and PAI-1 may be used as prognostic markers and also be helpful to make treatment decisions, especially for patients with lymph node-negative breast cancer. Copyright © 2013 by TUMOR.
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Objective: To investigate the inhibitory effect of Luffin-β-targeted fusion immunotoxin, which contains endoplasmic reticulum-resident signal fragment KDEL (Lys-Asp-Glu-Leu-COOH) and the uPAcs (cleavage site of urokinase-type plasminogen activator), on NSCLC (non-small cell lung cancer) cells. Methods: Luffin-β gene was cloned by RT-PCR (reverse transcriptase-polymerase chain reaction). Fused gene Luffin-β-KDEL-uPAcs was constructed by primer extension method, and inserted in pET-32a(+) vector to form the recombinant vector pET-32a(+)/Luffin-β-KDEL-uPAcs. After pET-32a(+)/Luffin-β-KDEL-uPAcs imported into Escherichia coli, the exression of fusion protein TELKP (Trx-EK-Luffin-β-KDEL-uPAcs) was induced, and then the TELKP was purified. EK (enterokinase) was used to digest TELKP to produce the targeting fused immunotoxin LKP (Luffin-β-KDEL-uPAcs). CCK-8 (cell counting kit-8), RT-PCR and Western blotting were employed to test the cytotoxic effect of LKP cleavaged by uPA (urokinase-type plasminogen activator) for setting free immunotoxin Luffin-β on NSCLC cells in vitro. Results: The recombinant vector pET-32a(+)/Luffin-β-KDEL-uPAcs could be induced to express the fusion protein TELKP, which contained Trx tag of vector pET-32a(+) and its relative molecular mass was about 4.88×104. The immunotoxin protein LKP, which contained 290 amine acids and its relative molecular mass was about 3.1 8×1104, could be produced after the fusion protein TELKP was digested by EK. The immunotoxin Luffin-β, which possessed cytotoxic effect on tumor cells, could be released from LKP protein cleavaged by uPA in vitro, and its cytotoxic effect was dose-dependent. Conclusion: Fused gene Luffin-β-KDEL-uPAcs and its prokaryotic express vector are successfully constructed. Recombinant fusion immunotoxin LKP, whose relative molecular mass is about 3.1 8×104, is successfully prepared. The immunotoxin Luffin-β, which possesses cytotoxic effect on tumor cells, can be released from LKP protein cleavaged by uPA in vitro. Copyright © 2013 by TUMOR.
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ObjectiveTo evaluate the efficacy of intravenous and intra-arterial thrombolysis with urokinase for acute cerebral infarction.Methods Fifty patients with acute cerebral infarction occurred within 6 hours were divided into two groups by random digits table method with 25 cases each:intravenous and intra-arterial thrombolysis group and intravenous thrombolysis group.The patients in intravenous and intra-arterial thrombolysis group were given 200 000 U urokinase by intravenous infusion for 30 minutes immediately after being hospitalized,and arterial thrombolysis was prepared at the same time.With cerebrovascular angiography,the thrombolytic therapy was carried out in the target vessel blocking points through micro-catheter.Urokinase dissolved in 0.9％ sodium chloride was infused at the rate of 10 000 U per minute,the total volume would not be more than 1 000 000 U.The patients in intravenous thrombolysis group were given 1 000 000 U urokinase in 100 ml 0.9％ sodium chloride by intravenous infusion within 60 minutes.The clinical efficacy after thrombolysis was assessed according to the National Institutes of Health stroke scale (NIHSS) score,the quality of life was judged by Barthel index (BI) score and the prognosis was evaluated by modified Rankin scale (mRS) score of 90 days after thrombolysis.ResultsThere was no significant difference between two groups before thrombolysis according to the NIHSS score (P ＞ 0.05).After thrombolysis,NIHSS scores in two groups showed a downward trend,but they were obviously lower in intravenous and intra-arterial thrombolysis group after 24 h,7 d and 14 d than those in intravenous thrombolysis group [(8.97±4.56) scores vs.(11.01±3.65) scores,(6.88±2.31) scores vs.(8.34±3.05) scores,( 4.06±3.02 ) scores vs.( 6.73±2.15 ) scores ] ( P ＜ 0.05 or ＜ 0.01 ).BI scores before thrombolysis between two groups had no significant difference(P ＞0.05),while BI score of 90 days after thrombolysis in intravenous and intra-arterial thrombolysis group [(79.55±19.64) scores] was higher than that in intravenous thrombolysis group [(69.31±21.35) scores](P=0.0162).The rate of mRS score 0-2 (good efficscy) in intravenous and intra-arterial thrombolysis group [72.0％(18/25) ] was obviously higher than that in intravenous thrombolysis group [ 52.0％ ( 13/25 ) ] (P =0.0198 ).ConclusionsIt is significantly effective to treat acute cerebral infarction by superselective intravenous and intra-arterial thrombolysis.Therefore,it is supposed to be an optimal option for treating acute cerebral infarction in the future.
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ObjectiveTo investigate the value for the clinical application of urokinase combined with Sodium Tanshion ⅡA in the treatment of cerebral thrombosis.Methods160 cases with cerebral thrombosis in our hospital were chosen.They were randomly divided into A group with 80 cases and B group with 80 cases.A group was the observation group (Tanshion ⅡA Urokinase combined treatment group),B group was the control group (urine kinase treatment group).2 weeks treatment was a course.The efficacy of treatment in the two groups at the end was taken for statistical analysis.ResultsThe neurological deficits were significantly improved in A and B group before and after treatment (P ＜ 0.05,there was statistically significant).The neurological deficit scores in A group after treatment was significantly lower than group B ( P ＜ 0.05,there was statistically significant).The total effective rate was 95 ％ by the treatment of urokinase and Tanshion Ⅱa in A group which was higher than group B ( P ＜ 0.05,there was statistically significant difference).ConclusionThe treatment of urokinase combined with Sodium Tanshion Ⅱa could improve neurological deficits and improve the clinical therapeutic effect.
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Objective To determine association between tongue carcinoma and polymorphism of urokinase-type plasminogen activator (PLAU) gene.Methods PLAU genotypes of 97 patients with tongue carcinoma and 91 health controls were examined by the PCR-RFLP method.Statistical analyses included a chi-square test for homogeneity and logistic regression analysis.Results The polymorphism in PLAU gene was rs2227564 C/T.Logistic analyses indicated that compared with CT and TT genotypes,CC genotype was risk factor for development of tongue carcinoma (adjusted OR =1.281,95 ％ CI 1.098-2.577,P =0.037).Conclusion PLAU polymorphism may be associated with development of tongue carcinoma.
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ObjectiveTo investigate the serum soluble urokinase-type plasminogen activator (suPAR)in patients with multiple myeloma,its relationship with the 2-year survival rate and its clinical significance in predicting the disease prognosis.MethodsEnzyme-linked immunosorbent assay was applied to determine the levels of suPAR of 40 initial diagnosed patients with MM and 30 healthy persons as healthy control group.The patients were divided into three groups:effective (13 cases),remission (19 cases) and invalid (8 cases).ResultsUsually there was suPAR expression [(233.47±83.22) pg/ml] in serum of the healthy adults.There was no statistical difference of the suPAR expression in effective group or remission group before treated [(257.60±32.47) pg/ml,(331.00±99.80) pg/ml] compated with healthy group (t =2.04,t =1.83,P ＞ 0.05),and that in the invalid group,serum levels of suPAR [(562.20±291.0) pg/ml] was statistically significant with that of the effective group and that of the healthy control group (t =3.92,t =1.93,P ＜ 0.05).Through monitoring 17 patients,the suPAR of patients before treatment [(437.65±131.43) pg/ml] was statistically significant with that of healthy control group (P ＜0.01) and effective group after treatment [(298.76±108.59) pg/ml] (P ＜0.01).Serum suPAR of more than 2-year-survival patients [(333.02±85.37) pg/nl] during initial diagnosis was not statistically difference with that of the healthy control group (t =1.81,P ＞ 0.05).Serum suPAR of less than 2-year-survival patients [(646.01±103.97) pg/ml] was statistically different with that of healthy control group (t =3.84,P ＜0.01) and that of more than 2-year-survival patient group (t =3.50,P ＜0.01).ConclusionThe suPAR value was correlated to the stability of multiple myeloma,and can be used for disease prognosis and estimation of survival time.And the high expression of suPAR was related to the adverse prognosis.
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Objective To study the expressions of S100A4 and urokinase plasminogen activator(uPA) in pancreatic cancer cells and their correlation with patients prognosis.Methods The expressions of S100A4 and uPA were examined in 63 surgical specimens of primary pancreatic carcinoma by suing immunohistochemistry PV methods,and correlation of their expressions and prognosis of pancreatic cancer was analyzed.Results ( 1 ) Positive immunostaining for S100A4 and uPA was observed in 74.6％ (47 cases) and 65.1％ (44 cases) of 63 pancreatic cancer samples respectively.(2) The positive expressions of S100A4 and uPA were significantly correlated in pancreatic cancer( P =0.000,r =0.567 ).( 3 ) The expression of S100A4 significantly correlated with TNM stages( P =0.002 ),lymph node metastasis ( P =0.002 ) and distant metastasis ( P =0.007 ).The expression of uPA had a significant correlation with TNM stages ( P =0.002),lymph node metastasis ( P =0.001 )and differentiation(P =0.003).(4) Kaplan-Meier survival analysis showed that the median survival (21 months) of patients with S100A4 ( - ) was significantly longer than the median survival ( 9 months) of the patients with S100A4( + )(P=0.000) ;the median survival(9 months) of patients with uPA( + ) was significantly shorter than the median survival ( 18 months) of the patients with uPA ( - ) ( P =0.000) ; the median survival(23 months)of 13 patients with S100A4( - )/uPA( - )was significantly longer than the median survival of other cases ( Log-rank test,x2 =54.444,P =0.000).( 5 ) Cox regression model ( x2 =53.974,P =0.000 )analysis suggested:the differentiation(P =0.004),lymph node metastasis(P =0.017) 、S100A4( + ) expression ( P =0.000) and uPA ( + ) expression ( P =0.001 ) were independent prognostic factors for pancreatic cancer.Conclusion S100A4 and uPA are highly expressed in pancreatic cancer cells,and S100A4 expression has positive correlation with uPA expression,which indicates that the overexpression of S100A4 and uPA maybe poor prognosis factors for pancreatic cancer patients.S100A4 maybe promote extracellular matrix and basement membrane degradation by up-regulation of uPA protein expression,and ultimately promote tumor invasion and metastasis,which is not favorable to prognosis.They may be potential indicators of metastasis and predictors for prognosis of pancreatic cancer.
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Objective To study the change of thrombosis in rabbits arteries by electron microscope after thromb was lyses by urokinase targeted microbubbles.Methods A total of 24 rabbits with plateletrich thrombi in the femoral artery were randomized into 4 treatment groups (n = 6) :(1) ultrasound alone (US) ; (2) urokinase alone (UK); (3) ultrasound, non-targeted microbubble and urokinase (US + M + UK) ;(4) ultrasound, platelet-targeted microbubble and urokinase (US + R + UK).Urokinase targeted microbubbles were in conjunction with the surface of commercial microbubbles (SonoVue) by direct conjugation method.US was simultaneously applied transcutaneously over the thrombus up to 30 min.The thrombolytic effect was based on ultrasound, blood flow and histological observations at 120 min post treatment.Results US + R + UK group was completed recanalization (P ＜ 0.001).Scanning electron microscope examination showed thrombosis of the fiber network structure damage.Conclusions The main electron microscope change of RGDS urokinase targeted microbubbles dissolve thromb is thrombus fibrin network structure damage and fibrin dissolution.
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ObjectiveTo study the curative effect and safety of low dose of urokinase (UK) combined with low molecular heparin calcium.MethodsSixty-four cases of sudden cardiac arrest patients were divided into treatment group and control group by random digits table with 32 cases each.Two groups were given cardiopulmonary resuscitation according to the 2005 international guide for cardiopulmonary resuscitation and emergency cardiovascular care.Early in the recovery,the patients in treatment group were pumped in vein with low dose of UK(200 000 U) and injected subcutaneous with low molecular heparin calcium (4100 U ) in 30 minutes.The rate of return of spontaneous circulation (ROSC),survival rate longer than 24 hours and 30 days in two groups and patients dying of bleeding or bleeding conditions in treatment group were observed.ResultsThere were 11 cases (34.4％) of ROSC in control group,and compared with 20 cases (62.5％) in treatment group,there was significant difference (P＜0.05).There were 5 cases (15.6％) of survival longer than 24 hours in control group,and compared with 13 cases(40.6％) in treatment group,there was significant difference (P ＜ 0.05 ).There were 2 cases (6.2％) of survival 30 days in control group,and compared with 8 cases (25.0％) in treatment group,there was significant difference (P＜ 0.01 ).Nobody had subcutaneous bleeding or other organ hemorrhage in control group.But there was I patient who had subcutaneous limited ecchymosis in the injection site in treatment group.The difference of fibrinogen before and after treatment in treatment group was statistically significant(P ＜ 0.01 ),but there was no significant difference in prothrombin time and platelet count before and after treatment in treatment group (P ＞ 0.05).ConclusionsIt is safe and effective in cardiopulmonary resuscitation with low dose of UK combined with low molecular heparin calcium.
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Objective To investigate the expression and influence to tumor angiogenesis of urokinase-type plasminogen activator (uPA) and vascular endothelial growth factor (VEGF) in esophageal carcinoma. Methods The expression of uPA and VEGF in the tissue of normal (18 cases) and esophageal carcinoma (68 cases) were evaluated by SP immunohistochemistry, CD34 was detected as marking tumor microvessel density (MVD). uPA and VEGF expression were assessed as to the pathologically biological features of esophageal cancer and to the influence to tumor angiogenesis. Results The positive rates of uPA were 27.8 % (5/18) and 70.6 % (48/68) in the tissue of normal and esophageal carcinoma, respectively, there was significant difference in two tissues (x2 =11.63, P 0.05), but associated with clinical stage, histologic grading and lymph node metastasis (P <0.05). Conclusion Rising expression levels of uPA and VEGF are common in esophageal carcinoma. Altered expression of uPA and VEGF may contribute to tumor angiogenesis of esophageal carcinoma, whose overexpression indicate worse prognosis.
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Objective To investigate the effect of amiloride on the invasion capacity of esophageal carcinoma EC9706 cell line in vitro and to elucidate its possible mechanism.Methods The invasion capacities of EC9706 cells pretreated with amiloride were measured by transwell chamber assay. The urokinase-type plasminogen activator (uPA) transcription were determined by RT-PCR.The protein expression of uPA were assessed by Western blot.Results After the EC9706 cells were pretreated with amiloride at different concentrations,the number of invaded cells was obviously less than those of control group with obvious dosage dependent pattern (96±7,78±6,57±6,33±4,15±3,F =43.46,P ＜ 0.01).The transcription levels of uPA mRNA and the protein expression levels of uPA in EC9706 cells decreased significantly compared with the control (mRNA:0.623±0.065,0.526±0.054,0.389±0.041,0.312±0.038,0.247±0.025,F =6.71,P ＜0.01; protein:0.732±0.064,0.644±0.057,0.533±0.058,0.391±0.036,0.267±0.043,F =6.71,P ＜0.01).Conclusion Amiloride inhibits the invasion capacity of esophageal carcinoma EC9706 cells.The mechanism might be associated with down-regulation of the expression of uPA.
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Objective To determine the effect of the combined use of urokinase and glycoprotein Ⅱb/Ⅲa-targeted microbubbles prepared by direct conjugation method to dissolve the thromb in vivo and analyse the velocity tracing change of blood flow and explore the possible mechanism. Methods A total of 42 rabbits with platelet-rich thrombi in the femoral artery were randomized into 7 treatment groups ( n = 6 in each group): 1) ultrasound alone (US); 2) ultrasound plus non-targeted microbubbles ( US + M); 3) urokinase alone (UK) ;4) ultrasound, non-targeted microbubble and urokinase (US + M + UK); 5) ultrasound plus platelet-targeted microbubble ( US + R); 6) platelet-targeted microbubble plus urokinase (R + UK); 7)ultrasound, platelet-targeted microbubble and urokinase (US + R + UK). A total of 6 ml of infusion liquor of Urokinase,RGDS and microbubbles (SonoVue) were mixed by 1 ∶ 1 ∶ 1 ratio by the direct conjugation method, infusion via vein within 20 min. Ultrasound was conducted to lyse the clot for 30 min. The recanalization and the velocity tracing change of blood flow in thrombolytic process were evaluated at 120 min post treatment. Results For US, UK, US + M, US + R and US + M + UK groups, recanalization was failed. The R + UK and US + R + UK was recanalizated ( P ＜0.001 ). The blood flow velocity tracing was small and low width in US,UK, US + M, US + R and US + M + UK groups. The wave was high width and disorderly under the thrombolysis therapy in the R + UK and US + R + UK. The thrombolytic effect was demonstrated by the high-width and disorderly resonance changes in the blood flow spectrum during the thrombolytic therapy of US + R + UK. Conclusions The blood flow spectrum of groups had different characteristics in vivo when thrombus was issolved,ultrasonic resonance might be the possible mechanism.