Intravitreal fibrin clots were produced by intravitreal injection of 0.2 ml autologous plasma in 18 rabbit eyes. Subsequently these eyes were treated by intravitreal injection of either tissue plasminogin activator(t-PA) or saline. In the t-PA(12.5mu;g) group(n=10),intravitreal fibrin clots of 6 eyes cleared up within 6 hours, and that of the other 4 eyes within 1 day. In the saline group( n=7), the complete clearallce was not seen after 7 days. The difference of time between two groups was significant ( P＜0. 05), and no evidence of toxic effect was observed as measured by slit-lamp biomicrocopy, ERG, light microcopy and transmission electron microscopy.One eye treated with 100mu;g t-PA also resulted in a total clearance within 6 hours,but retinal toxicity was demonstrated with ophthalmoscopy and light microscopy. （Chin J Ocul Fundus Dis,1994,10:14-16）
Objective To observe the inhibitory effects of local co-transfection of tissuetype plasminogen activator(tPA) gene and proliferating cell nuclear antigen antisense oligodeoxynucleotides(PCNA-ASODN) on the intima proliferation and restenosis of autograft artery in rabbits. Methods One hundred and twenty male Zelanian rabbits were randomly divided into four groups(n=30, in each group): control group, PCNA-ASODN group, tPA group and tPA+PCNAASODN group. The left and right external iliac arteries (length 1.0 cm) were transplanted reciprocally. The transplanted arteries were respectively soaked in lipofection, PCNAASODN, pBudCE4.1/tPA and pBudCE4.1/tPA+PCNA-ASODN solution about 15 minutes. The transplanted arteries were sutured with 9-0 sutures soaked in PCNA-ASODN and pBudCE4.1/tPA solution. Each group were divided into five subgroups(n=6, in each subgroup) according to the sacrifice time (3 d, 7 d, 14 d, 28 d and 56 d after operation). On every sacrifice time point, the vascular specimens were harvested. The thrombocyte assembling and thrombus forming lining vessel wall were observed by scanning electron microscope. The pathological morphology of transplanted arteries were observed under microscope(HE). The intimal areas and stenosis ratio(%) of transplanted arteries were calculate and analyzed statistically among groups by computer system. The mRNA expression of tPA gene in transplanted ressel wall was detected with vevere transcriptionPCR(RT-PCR). The number of PCNA positive cells in transplanted vessel wall was counted by SP immunochemisty.Results The mRNA expression of tPA gene in the transplanted vessel wall in tPA and tPA+PCNA-ASODN groups was higher than that of the other two groups(P＜0.01).The number of PCNA positive cells in the transplanted arteries in PCNAASODN, tPA and tPA+PCNAASODN groups were significantly lower than that of control group(P＜0.05，P＜0.01). The intimal areas and degrees of luminal stenosis of PCNAASODN, tPA and tPA+PCNAASODN groups were lower than those of control group(P＜0.05，P＜0.01), and those of tPA＋ PCNA-ASODN group were lower than those of PCNA-ASODN and tPA groups(P＜0.05). Scanning electron microscopy showed that there were a few thrombocytes lining the vessel wall of tPA group and tPA+PCNAASODN group and no thrombus, whereas there were abundant thrombocytes and thrombi lining the vessel wall of the control group. Conclusion Co-transfection of tPA gene and PCNA-ASODN can effectively inhibit the proliferation of VSMC, hyperplasia of intima and restenosis of transplanted artery.
ObjectiveTo observe the clinical effect of intravitreal injection of tissue plasminogen activator (t-PA), ranibizumab and C3F8 in the treatment of early submacular hemorrhage (SMH) induce to polypoid choroidal vasculopathy (PCV).MethodsThe clinical data of 20 eyes of 20 patients with early SMH induce to PCV were enrolled in this study. The duration of bleeding in the eye was 7 to 28 days, and the mean duration of bleeding was 14.8±5.6 days. All eyes are measured using the Snellen chart best corrected visual acuity (BCVA), logarithm of the minimum angle of resolution (logMAR) was used to calculate visual acuity. Measure central retinal thickness (CRT) and central retinal pigment epithelial detachment (PED) thickness using frequency-domain optical coherence tomography. The average logMAR BCVA of eyes was 1.73±0.91; the mean CRT was 620.0±275.8 μm; the average central PED thickness was 720.3±261.9 μm. All eyes receive intravitreal injection of t-PA, ranibizumab and C3F8. The intravitreal injection of ranibizumab was administered once a month for 3 consecutive months, followed by an on-demand treatment plan. Mean follow-up time was 9.9±3.6 months. The changes in BCVA, CRT, central PED thickness and clearance degree of SMH at 6 months after treatment were observed.ResultsOn the 6 months after treatment, the average logMAR BCVA, CRT and central PED thickness of the eyes were respectively 0.42±0.37, 290.2±97.4 μm and 41.6±78.1 μm. Compared with baseline, the after treatment BCVA was significantly increased (F=38.14, P=0.000), but the CRT and central PED were significantly decreased (F=7.48, 75.94; P=0.000, 0.000). Among the 20 eyes, 16 eyes of SMH was completely cleared, accounting for 80%;4 eyes was partially cleared, accounting for 20%. No recurrence and systemic or local complications occurred during follow-up of all eyes.ConclusionIntravitreal injection of t-PA, ranibizumab, and C3F8 in the treatment of early SMH induce to PCV can effectively remove SMH, improve vision, reduce CRT and central thickness of PED.
Objective To explore the effect of xue-shuan-tong(panax notoginsang saponins,PNS)or isovalaemic haemodilution(IHD)and PNS combining IHD treatment on activities of fibrinolysis and hemorrheology in patients with retinal vein occlusion (RVO). Methods Seventy-three patients with RVO were allocated at random to 3 groups which were treated with PNS,IHD and PNS combining IHD.The activities of t-PA and PAI,rheological parameters and visual acuity before and after treatment were observed. Results At the end of treatment,significantly increased activity of t-PA and decrease of PAI was found in combined treatment group and PNS group,but the difference before and after treatment was not significant in IHD group.Furthermore,except the plasma viscosity in IHD group,the other hemorrheological parameters in all the petients of 3 groups revealed to be improving.One month after treatment,the parameters return completely to normal in both PNS and IHD groups; while the whole blood apparent relative viscosity in low shear rate,RBC aggregation and RBC deformability maintained still in lower level,and also the visual acuity resumed better and quicker in combined group. Conclusion Combined treatment of PNS and IHD can both regulate the activity of fibrinolysis and decrease the blood viscosity of patients with RVO for a period of relatively long time and increase the effect of treatment. (Chin J Ocul Fundus Dis,1998,14:7-9)
【Abstract】ObjectiveTo investigate the relationship between the expression of urokinase-type plasminogen activator (uPA) mRNA and breast cancer, lymph node metastasis. MethodsSixty patients with breast tumor were selected randomly and the expression of uPA mRNA was detected with RT-PCR. The patients were divided into benign group (18 cases) and malignant group (42 cases) which included 22 cases with lymph node metastasis and 20 cases without lymph node metastasis. The relationship between uPA mRNA expression and breast cancer, lymph node metastasis was analyzed. ResultsAmong these 18 benign tumors, low expression of uPA mRNA was found in 2 cases and the others were negative. While in 42 cases of malignant tumor, uPA mRNA were positive in 22 cases of lymph node metastasis, 16 of which were high expression, 5 of which were moderate expression, and 1 was low expression. uPA mRNA were positive in 18 of 20 cases of nonmetastatic lymph node, 1 of which was high expression, 5 of which were moderate expression and 12 of which were low expression, the other 2 were negative expression. The expression of uPA mRNA had significant difference between benign and malignant tumors (P＜0.05). The expression in lymph node metastasis was much higher than no lymph node metastasis (P＜0.05). ConclusionThe expression of uPA mRNA in malignant breast cancer is obviously higher than that in benign breast tumor. The expression tensity of uPA is highly relevant to lymph node metastasis in malignant breast cancer, which can provide evidence for clinical staging and therapy.
Objective To investigate the expression of urokinase-type plasminogen activator (uPA) mRNA in gastric cancer tissues and cancer-adjacent tissues and the relationship between its expression and biologic behavior of tumor. Methods Fourty-eight cases with gastric cancer were detected for the expression of uPA mRNA by fluorogenic probe quantitative reverse transcription polymerase chain reaction (RTPCR). Results The positive expression rate of uPA mRNA was 83.3%, 25.0%, 93.8% and 62.5% in gastric cancer tissues,cancer-adjacent tissues, gastric cancer tissues with lymph node metastasis and with non-lymph node metastasis respectively. Expression of uPA mRNA was positively related with the invasion depth of gastric cancer. Conclusion Expression of uPA mRNA is significantly increased in gastric cancer and it can be used as an indicator to judge the metastasis and prognosis of tumor.
ObjectiveTo observe the clinical effect of super-selective ophthalmic artery or selective carotid artery thrombolytic therapy for central retinal artery occlusion (CRAO). MethodsTwelve CRAO patients (12 eyes) were enrolled in this study. The patients included 7 males and 5 females. The age was ranged from 19 to 68 years old, with an average of (50.0±3.5) years. The disease duration was from 8 to 72 hours, with a mean of 18 hours. All the patients were received the treatment of super-selective ophthalmic artery or selective carotid artery thrombolysis with urokinase (total 0.20-0.4 million U) and injection of papaverine 30 mg. Five patients received the treatment of super-selective ophthalmic artery thrombolytic therapy, 7 patients received the treatment of selective carotid artery thrombolytic therapy (4 patients because of the financial issues, 3 patients because of thin ophthalmic artery). According to the visual acuity of post-treatment and pre-treatment, the therapeutic effects on vision were defined as effective markedly (improving three lines or more), effective (improving two lines) and no effect (no change or a decline). According to the arm-retinal circulation time (A-Rct) and filling time of retinal artery and its branches (FT) on fluorescence fundus angiography (FFA), the therapeutic effects on retinal circulation were defined as effective markedly (A-Rct 15 s, FT 2 s), effective (A-Rct was improved but in the range of 16-20 s, FT was in 3-8 s) and no effect (A-Rct was improved but 21 s, FT 9 s). ResultsThe vision changes showed effective markedly in 5 eyes (41.7%), effective in 5 eyes (41.7%), no effect in 2 eyes (16.6%). The total therapeutic efficiency on vision was 83.4%. The retinal circulation was improved in all eyes after treatment, including effective markedly in 8 eyes (67.0%), effective in 4 eyes (33.0%). The total therapeutic efficiency on retinal circulation was 100.0%. No complications occurred in these 12 patients during the treatment or follow-up, such as puncture site hematoma, intracranial hemorrhage, cerebral embolism, eye movement abnormalities, retinal and vitreous hemorrhage. ConclusionSuper-selective ophthalmic artery and selective carotid artery thrombolytic therapy were effective in the treatment of CRAO.
ObjectiveTo investigate the therapeutic effects of thrombolysis infusion via microcatheter on the treatment of central retinal artery occlusion(CRAO). MethodsUrokinase (UK) was directly infused via ophthalmic artery (OA) by microcatheter (6 patients) or via intravenous (7 patients) to dissolve the thrombus. The patency of the artery was evaluated by fundus fluorescein angiography (FFA), and the effect of fibrinolytic activity on the systemic changes was observed by blood biochemical examination simultaneously. ResultsIn 6 patients in the microcatheter group, 5 had completely and 1 had partly reopened OA on the morrow of UK infusion with the patency rate of 83.33%, while in 7 patients in vein group, 3 completely reopened, 2 partly reopened and 2 obstructed OA were found with the patency rate of 42.86%. The difference between the two groups was significant. No obvious change of index of blood coagulation system was found in catheter group, which had great disparity compared with the vein group.ConclusionUrokinase infusion via microcatheter in CRAO has better therapeutic impact and smaller effect on systemic action. (Chin J Ocul Fundus Dis, 2005,21:16-19)
Objective Investigate the effect and treatment prospects of urokinase-type plasminogen activator receptor（uPAR）in human epidermal growth factor receptor-2 （HER-2） positive breast cancer. Method Aricals related effect of uPAR in HER-2 positive breast caner were retrieved through Pubmed， and the role of uPAR was reviewed. Results uPAR played a very important role in the HER-2 positive breast cancer， anti-uPAR monomer or uPAR binding inhibitors could inhibit the growth， invasion and metastasis of breast cancer cells. Conclusion uPAR is one of the effective target for breast cancer， and it provides a new breakthrough in the treatment of HER-2 positive breast cancer.
Urokinase plasminogen activator receptor (uPAR) is a membrane protein which is attached to the cellular external membrane. The uPAR expression can be observed both in tumor cells and in tumor-associated stromal cells. Thus, in the present study, the human amino-terminal fragment (hATF), as a targeting element to uPAR, is used to conjugate to the surface of superparamagnetic iron nanoparticle (SPIO). Flowcytometry was used to examine the uPAR expression in different tumor cell lines. The specificity of hATF-SPIO was verified by Prussian blue stain and cell phantom test. The imaging properties of hATF-SPIO were confirmed in vivo magnetic resonance imaging (MRI) of uPAR-elevated colon tumor. Finally, the distribution of hATF-SPIO in tumor tissue was confirmed by pathological staining. Results showed that the three cells in which we screened, presented different expression characteristics, i.e., Hela cells strongly expressed uPAR, HT29 cells moderately expressed uPAR, but Lovo cells didn't express uPAR. In vitro, after incubating with Hela cells, hATF-SPIO could specifically combined to and be subsequently internalized by uPAR positive cells, which could be observed via Prussian blue staining. Meanwhile T2WI signal intensity of Hela cells, after incubation with targeted probe, significantly decreased, and otherwise no obvious changes in Lovo cells both by Prussian blue staining and MRI scans. In vivo, hATF-SPIO could be systematically delivered to HT29 xenograft and accumulated in the tumor tissue which was confirmed by Prussian Blue stain compared to Lovo xenografts. Twenty-four hours after injection of targeting probe, the signal intensity of HT29 xenografts was lower than Lovo ones which was statistically significant. This targeting nanoparticles enabled not only in vitro specifically combining to uPAR positive cells but also in vivo imaging of uPAR moderately elevated colon cancer lesions.