肝细胞癌癌组织中uPA及其受体的表达及意义

目的 探讨肝细胞癌(HCC)的发生机制.方法 通过组织芯片及免疫组化法测定HCC癌组织中uPA及其受体(uPAR)的表达,并与肝硬化及正常肝组织比较. 结果 uPA在HCC、肝硬化、正常肝组织中的阳性表达率分别为74.0%、46.7%、20%,两两比较,P均＜0.05;随HCC分期进展及肿瘤直径增大,uPA表达阳性率逐渐升高.uPAR在HCC、肝硬化、正常肝组织中的阳性表达率分别为70.0%、63.3%、15.0%,与正常肝组织比较,P均＜0.05;uPAR阳性表达率随HCC分期进展表达逐渐上升,与肿瘤直径无密切关系.相关分析示,uPA和uPAR具有明显相关性.结论 HCC发生和发展是多因素共同作用的结果,其机制可能为uPA及uPAR高表达.     

肝细胞癌中u-PA和MMP-9的表达及意义

目的探讨尿激酶型纤溶酶原激活物(u-PA)、基质金属蛋白酶-9(MMP-9)在肝细胞癌中的表达及其临床意义。方法采用免疫组化法对80例肝细胞癌标本进行u-PA和MMP-9检测,并以12例肝移植供肝作为阴性对照。结果u-PA及MMP-9在肝癌中的表达阳性率分别为83.75%、76.25%,明显高于癌旁组织(33.75%、30%),P<0.01。u-PA及MMP-9在伴转移及癌栓形成肝癌的阳性表达率分别为91.43%、85.71%,明显高于非转移者(77.78%、68.89%),P<0.05;且u-PA、MMP-9阳性表达间呈正相关。结论u-PA和MMP-9的高表达与肝细胞癌的侵袭转移有关,二者联检有助于判断肝细胞癌的预后。     

乳腺癌组织中Maspin、uPA的表达及意义

目的探讨新的丝氨酸蛋白酶抑制剂基因（Maspin）蛋白、尿激酶型纤溶酶原激活物（uPA）在人乳腺癌组织中的表达及意义。方法选择乳腺癌组织标本79份（乳腺癌组）、乳腺纤维腺瘤组织标本31份（腺瘤组）、正常乳腺组织标本34份（正常组）,采用免疫组化SP法检测各组Maspin蛋白、uPA的表达,并分析两指标在乳腺癌中表达的相关性。结果乳腺癌组、腺瘤组、正常组Maspin蛋白的阳性表达率分别为30．4％、67．7％、97．1％,乳腺癌组、腺瘤组明显低于正常组,乳腺癌组明显低于腺瘤组（P均〈0．05）;uPA的阳性表达率分别为64．5、32．2％、26．5％,乳腺癌组、腺瘤组明显高于正常组,乳腺癌组明显高于腺瘤组（P均〈0．05）。乳腺癌组织中Maspin蛋白表达与uPA表达呈负相关。结论Maspin低表达和uPA高表达在乳腺癌发生、发展中起重要作用。     

uPA、uPAR和肝癌的研究进展

尿激酶型纤溶酶原激活物（ urokinase type plasminosen activator, uPA ） 及其特异性受体（urokinase type plasminogen activator receptor,uPAn）介导的纤维蛋白溶解系统在恶性肿瘤的浸润和转移中起重要作用。     

uPA、uPAR和uPA／uPAR与肝癌发生的研究进展

尿激酶型纤溶酶原激活物（urokinase type plasminogen activator,uPA）及其特异性受体（urokinase type plasminogen activatorreceptor,uPAR）介导纤维蛋白溶解系统在肿瘤的浸润和转移中发挥重要作用。近年研究表明,uPA、uPAR不仅在肿瘤的浸润和转移中发挥重要作用,而且与肝硬化纤维化进程中恶变趋势及肝的出凝血系统有关,已经成为肝癌研究中的新热点。     

宫颈鳞癌组织中uPA、uPAR的表达变化及意义

目的检测宫颈鳞癌组织中尿激酶型纤溶酶原激活物（uPA）及其受体（uPAR）的表达,并探讨其意义。方法采用免疫组织化学法分别检测正常宫颈组织、宫颈非典型增生组织及宫颈癌组织中的uPA、uPAR。结果uPA、uPAR的表达程度宫颈癌组织高于非典型增生宫颈组织,非典型增生宫颈组织高于正常宫颈组织（P均〈0．05）。宫颈癌组织中uPA、uPAR表达程度与临床分期和淋巴结转移有关（P均〈0．05）。结论宫颈癌组织中uPA、uPAR表达升高。其可能与宫颈癌的发生、发展、浸润、转移有关。     

uPA和MMP-9在膀胱移行细胞癌癌组织中的表达及意义

应用免疫组化法检测47例膀胱移行细胞癌(BTCC)患者癌组织中尿激酶型纤溶蛋白酶原激活物(uPA)和基质金属蛋白酶-9(MMP-9)的表达水平,并行相关性分析. 结果uPA、MMP-9在BTCC癌组织中的表达率分别为76.6% 、78.9%;随病理分级增高,uPA表达率增高,MMP-9则先下降后增高,病理分期越高,二者阳性表达率越高.uPA与MMP-9均阳性的表达率为57.4%, 相关分析示MMP-9和uPA呈明显正相关.认为uPA与MMP-9联合检测有助于判断BTCC患者的预后及复发.     

VEGF、uPA及uPAR与胃癌侵袭和转移的相关性

目的探讨血管内皮生长因子(VEGF)、尿激酶型纤溶酶原激活物(uPA)及其受体(uPAR)与胃癌侵袭、转移的关系及其相关性。方法采用免疫组化SP方法检测198份胃癌组织标本(胃癌组)、60份正常胃黏膜组织标本(对照组)VEGF、uPA、uPAR表达。结果与对照组比较,胃癌组VEGF呈高表达,并与浸润深度、淋巴结转移和临床分期呈正相关,与肿瘤的分化程度呈负相关,P均<0.05;胃癌组uPA和uPAR呈高表达,与病理分级、浸润深度、淋巴转移、临床分期有关,P均<0.05。胃癌组VEGF与uPA表达呈正相关,P<0.01;uPA与uPAR表达呈正相关,P<0.01。结论 VEGF、uPA、uPAR在胃癌发生、发展、侵袭和转移中起促进作用;三者相互促进,相互协调,关系密切。三者均可作为胃癌诊断和预后估计的指标及胃癌治疗的新靶点。     

尿激酶型纤溶酶原激活物途径在大鼠酒精性肝纤维化形成中的作用

目的 通过观察尿激酶型纤溶酶原激活物(uPA)及其抑制物(PAI-1)在大鼠酒精性肝纤维化形成中的动态变化,探讨uPA纤溶途径在酒精性肝纤维化形成中的作用.方法 雄性SD大鼠随机分为空白组、四氯化碳(CCl4)组和造模组.采用56度二锅头酒、玉米油、吡唑混合物灌胃联合腹腔注射CCl4橄榄油溶液(CCl4∶橄榄油=1∶3...     

胃癌组织Maspin,uPA,MMP-7表达的意义

目的:观察胃癌及正常胃黏膜Maspin,uPA, MMP-7表达的意义．方法:应用免疫组化SP法检测胃管状腺癌30 例,胃印戒细胞癌30例,正常胃黏膜组织20例中Maspin,uPA,MMP-7的表达情况．结果:在胃管状腺癌中Maspin,uPA,MMP-7 阳性表达率分别为50％,70％和80％;胃印戒细胞癌中阳性表达率分别为46．7％,76．7％和 90％;正常胃黏膜组织中阳性表达率分别为 90％,35％和30％．Maspin的表达与浸润深度、淋巴结转移相关,而与肿块的大小和TNM分期无关．uPA和MMP-7的表达与浸润深度、淋巴结转移、TNM分期相关,而与肿块的大小无关．Maspin的表达与uPA和MMP-7的表达呈负相关(P=0．012,r=-0．322;P=0．008,r= -0．341);uPA的表达与MMP-7的表达呈正相关 (P=0．034,r=0．274)．结论:Maspin在胃癌中表达下调,uPA和 MMP-7在胃癌中过表达,他们在胃癌的浸润转移中起重要作用,可作为反应胃癌病理生物学行为的有效指标．     

Clinical significance of urokinase-type plasminogen activator activity in hepatocellular carcinoma

BACKGROUND AND METHODS: The plasminogen activation system plays a crucial role in the process of cancer invasion and metastasis. To evaluate the most effective factor in the invasion, metastasis and prognosis of hepatocellular carcinoma (HCC), we examined urokinase-type plasminogen activator (uPA), plasminogen activator inhibitor (PAI)-1, PAI-2 and uPA activity by enzyme-linked immunosorbent assays (ELISA) in HCC tissues obtained from 46 patients. The results were compared with the patients' clinicopathological features and prognoses. RESULTS: Of the clinicopathological features, only histological portal involvement or intrahepatic metastasis, or both (INV), was significantly correlated to the disease-free survival rates (DFS; P < 0.05). The levels of uPA, PAI-1 and PAI-2 antigens were significantly associated with INV and histological grade. The DFS was not different, however, between cases with uPA, PAI-1 and PAI-2 values above and below the median. The high levels of uPA activity were closely related to INV (P < 0.001), and the activity gradually raised histological grades (P < 0.0001). The DFS was significantly different between patients with uPA activity below and above the median (0.70 ng/mL; P = 0.0092); it was also significantly different between such patients without INV (P < 0.05). CONCLUSIONS: Urokinase-type plasminogen activator activity may be the most sensitive factor affecting HCC invasion in the plasminogen activation system and a strong predictor for the recurrence of HCC. We suggest that cases with uPA activity of more than 0.70 ng/mL should be carefully followed up for possible HCC recurrence.     

Hypofibrinolysis in patients with hypercoagulability: The roles of urokinase and of plasminogen activator inhibitor

The prevalence of abnormalities of fibrinolysis in patients with venous thromboembolism is as yet unknown. Defined abnormalities include congenital dysfunction and deficiency of plasminogen, and probably impaired plasminogen activation secondary to elevated levels of plasminogen activator inhibitor type 1 (PAI-1) or to impaired release of tissue plasminogen activator (tPA). In this preliminary study, we analyzed plasma samples from 21 patients for whom an investigation for possible thrombophilia was requested. Twenty of the patients had venous thromboembolism, and one had arterial thrombosis at an early age. Two patients had deficiency of protein C or protein S, but no other recognized biochemical disturbances related to thrombophilia were identified. Patient samples and plasma from 25 normal controls were assayed for tPA activity, PAI-1 activity, and urokinase (uPA) activity and antigen. tPA activity and antigen were not significantly different in patients than in controls. PAI-1 activity was significantly greater in patients (P < 0.0001). uPA activity was not different in the two groups. However, uPA antigen was significantly reduced in patients compared to controls (P = 0.001). These data suggest that hypofibrinolysis leading to a risk of thrombosis may be caused not only by elevated PAI-1 activity but also by reduced total uPA concentration. © 1993 Wiley-Liss, Inc.     

Chromosomal localization of the human urokinase plasminogen activator receptor and plasminogen activator inhibitor type-2 genes: Implications in colorectal cancer

Abstract Activation of the proenzyme of urokinase (uPA) on the surface of cancer cells has been implicated in the initiation of focal proteolytic mechanisms that permit invasion and metastasis by colon cancers. The activity of uPA on the cell surface appears to be a function of the number of uPA-specific receptors (uPAR) and the extent of inhibition of uPA by plasminogen activator inhibitors (PAI). The mapping of the genes coding for uPAR, and for PAI-2, was performed to determine whether their chromosomal localization suggested their involvement in the genetic alterations associated with cancer cell DNA.
This study confirms the localization of the human urokinase plasminogen activator receptor gene to chromosome 19q and, using in situ hybridization, provides a precise localization to chromosome 19q13.2. In addition, our results confirm the previous allocation of the human plasminogen activator inhibitor-2 gene to a location 18q21.3 → 18q21.1, a location that corresponds to the commonest (>70%) somatic deletions found in colorectal carcinomas. The mapping of the uPAR and PAI-2 genes enables the elucidation of their possible involvement in the genetic alterations that determine the invasive and metastatic phenotypes in colorectal cancer.     

Urokinase type plasminogen activator receptor expression in colorectal neoplasms

Background—The urokinase type plasminogenactivator receptor (uPAR) may play a critical role in cancer invasionand metastasis.
Aims—To study the involvement of uPAR incolorectal carcinogenesis.
Methods—The cellular expression and localisationof uPAR were investigated in colorectal adenomas and invasivecarcinomas by in situ hybridisation, immunohistochemistry, and northernand western blot analyses.
Results—uPAR mRNA expression was found mainly inthe cytoplasm of dysplastic epithelial cells of 30% of adenomas withmild (19%), moderate (21%), and severe (47%) dysplasia, and in that of carcinomatous cells of 85% of invasive carcinomas: Dukes' stages A(72%), B (93%), and C (91%). Some stromal cells in the adjacent neoplastic epithelium were faintly positive. Immunoreactivity for uPARwas detected in dysplastic epithelial cells of 14% of adenomas and incarcinomatous cells of 49% of invasive carcinomas. uPAR mRNA andprotein concentrations were significantly higher in severe than in mildor moderate dysplasia (p<0.05); they were notably higher in Dukes'stage A than in severe dysplasia (p<0.05), and significantly higher inDukes' stage B than in stage A (p<0.05), but those in stage B werenot different from those in stage C or in metastatic colorectalcarcinomas of the liver.
Conclusions—Colorectal adenoma uPAR, expressedessentially in dysplastic epithelial cells, was upregulated withincreasing severity of atypia, and increased notably during thecritical transition from severe dysplasic adenoma to invasivecarcinoma. These findings implicate uPAR expression in the invasive andmetastatic processes of colorectal cancer.

Keywords:urokinase type plasminogen activator receptor; colorectal adenoma; colorectal cancer; adenoma-carcinoma sequence

     

腺病毒介导的人uPA体外转染大鼠骨髓源性肝干细胞的研究

目的评价携带人uPA基因的腺病毒(AduPA)转染骨髓源性肝干细胞(BDLSC)的效率,在BDLSC中的表达及其对BDLSC增殖和分化的影响。方法利用淤胆型肝损伤大鼠模型和含5%淤胆血清病理条件培养液筛选和扩增BDLSC,采用荧光显微镜检测AduPA的转染效率,采用Westernblotting法检测uPA在BDLSC中的表达,采用MTT法和免疫细胞化学法分别检测转染AduPA的BDLSC的增殖和分化变化。结果随着MOI的增高,转染效率明显增高,当MOI为500时,转染效率达92.6±2.2%,转染3天后的人uPA在BDLSC稳定表达,且转染AduPA对BDLSC的增殖和分化无明显影响。结论BDLSC可能是一种良好的基因载体细胞,可携带uPA用于肝纤维化的治疗研究。     

肝细胞癌尿激酶型纤溶酶原激活物受体mRNA、VEGF和c-erbB2的表达及意义

探讨尿激酶型纤溶酶原激活物受体（UPAR）mRNA、血管内皮细胞生长因子（VEGF）和癌基因c—erbB2在肝细胞癌（HCC）的表达与其病理学特性和肿瘤转移的关系。采用原位杂交方法检测肝细胞癌UPA mRNA表达,免疫组化法检测VEGF和c—erbB2的表达。肝癌转移组的UPAR mRNA、VEGF和c—erbB2阳性表达率及表达强度均明显高于无转移组,二者相比均有显著性差异（P〈0．05）,但它们的表达与肝癌的大小、分化程度却无关;UPAR mRNA与VEGF及c—erbB2的表达强度均呈正相关（r=0．656、0．653,P〈0．05）。UPA mRNA、VEGF和c—erbB2的表达可作为肝细胞癌的侵袭表型、判断疗效以及估计预后的重要指标。     

单核细胞尿激酶型纤溶酶原激活物受体表达水平与冠状动脉粥样硬化斑块稳定性的关系

目的探讨不同临床类型的冠状动脉粥样硬化性心脏病患者外周血单核细胞尿激酶型纤溶酶原激活物受体(uPAR)表达水平的差异及其在治疗前后的变化,并观察该指标与术后心血管事件的相关性。方法连续入选经冠状动脉造影证实的冠心病患者136例,其中包括急性冠脉综合征(ACS)85例、稳定型心绞痛(SAP)51例,另选20例健康志愿者作为对照。留取全血标本,用流式细胞仪检测各组患者外周血单核细胞uPAR的表达水平。观察ACS组经皮冠状动脉介入(PCI)治疗24,48h,3个月后外周血单核细胞uPAR表达水平的变化。随访ACS组患者2年,记录主要心血管事件的发生情况。结果 ACS组uPAR表达水平较SAP组及健康志愿者组均显著升高(P0.01),ACS组PCI术后3个月的uPAR表达水平较术前有显著下降(P0.01)。85例ACS患者平均随访(20.46±2.45)个月,术后发生主要心血管事件24例,事件组单核细胞uPAR表达水平显著高于无事件组(P0.01)。应用多因素logistic回归分析发现,单核细胞上uPAR的表达水平与术后主要心血管事件显著相关(P0.01)。结论 ACS患者单核细胞uPAR的表达水平较SAP患者显著升高,ACS患者uPAR的表达水平与主要心血管事件具有明显相关性,单核细胞uPAR的表达水平是冠心病临床病情严重程度的一个敏感指标,对于判断动脉粥样斑块的稳定性以及心血管疾病的预后有重要价值。     

Expression of urokinase-type plasminogen activator receptor and plasminogen activator inhibitor-1 in gastric cancer

In gastric cancer, the urokinase-type plasminogen activator (uPA) system plays important roles in invasion and metastasis, processes which entail proteolysis and adhesion. Both the urokinasetype plasminogen activator receptor (uPAR) and the plasminogen activator inhibitor-1 (PAI-1) are thought to be important factors in this system. To clarify the relationship between these two factors and gastric cancer invasiveness, we evaluated the expression of uPAR and PAI-1 in 91 cases of gastric cancer by immunohistochemistry and in situ hybridization. Urokinase-type plasminogen activator receptor-mRNA, PAI-1-mRNA, uPAR and PAI-1 protein were diffusely distributed in the cytoplasm of the cancer cells and concentrated at invasive foci. Urokinase-type plasminogen activator receptor protein expression correlated with lymphatic, venous invasion (P<.01) and lymph node metastasis (P<0.05); uPAR-mRNA expression correlated with lymphatic, venous invasion and lymph node metastasis (P<0.05). Plasminogen activator inhibitor-1 protein expression correlated with lymphatic, venous invasion, lymph node metastasis and depth of invasion (P<0.01); PAI-1-mRNA expression was linked to lymphatic, venous invasion (P<0.01), lymph node metastasis and depth of invasion (P<0.05). This suggests that the proteolytic activity of uPAR and the cellular motility of PAI-1 in gastric cancer cells may determine penetration of lymphatic and blood vessels, whereby lymph node metastasis may be promoted and that the promotion of cellular motility by PAI-1 may influence the depth of cancer invasion.