可溶性尿激酶受体与肿瘤

尿酶受体（uPAR)是一种多功能受体，主要介导纤溶酶原的活化，它与肿瘤的生长、侵袭、转移过程密切相关。检测肿瘤患者血浆或血清中可溶性尿激酶受体（suPAR)有助于评估肿瘤患者的病情和预后。通过阻止尿激酶（uPA)与其受体的结合，可以抑制肿瘤的侵袭和转移，达到治疗的目的。     

肿瘤患者胸水可溶性尿激酶受体检测及其临床意义

目的　了解良、恶性胸水中可溶性尿激酶受体 (suPAR)的水平及其与肿瘤患者病情和预后的关系。方法　放射免疫分析法检测 2 6例恶性胸水及 10例炎性胸水患者suPAR水平 ,并与 2 1名正常人 (对照组 )对照。结果　恶性胸水、炎性胸水与正常血浆suPAR水平分别为 (4 .3 6±2 .12 ) μg/L、(2 .64± 1.0 5 ) μg/L和 (1.73± 0 .96) μg/L ,炎性胸水suPAR水平高于对照组 (P <0 .0 5 ) ,而恶性胸水suPAR水平又高于炎性胸水 (P <0 .0 5 )。恶性胸水suPAR水平还显示出与患者预后相关。结论　检测suPAR水平有助于鉴别胸水的良、恶性及判断恶性肿瘤患者的预后     

阵发性睡眠性血红蛋白尿症患者粒细胞及血浆尿激酶受体的检测

目的了解阵发性睡眠性血红蛋白尿症(PNH)患者体内尿激酶受体(uPAR)的表达水平,并探讨uPAR检测在PNH诊断中的临床意义.方法用流式细胞仪检测20例PNH患者粒细胞表面uPAR、CD55、CD59的表达水平,并与21例正常人、59例其他贫血患者(18例自身免疫溶血性贫血、6例其他溶血性贫血、26例慢性再生障碍性贫血、9例缺铁性贫血)比较;同时采用免疫放射分析(IRMA)测定PNH患者与正常人血浆可溶性uPAR(suPAR)的水平.结果 20例PNH患者中uPAR 、CD55、CD59表达水平显著降低,且与正常人uPAR表达下限不重叠.在PNH患者中还存在峰型异常[双峰和(或)峰拖尾].而57例其他贫血患者中粒细胞表面uPAR的表达水平无改变.PNH患者血浆suPAR水平为(4.04±2.47 )μg/L,明显高于正常人的(1.73±0.96 )μg/L水平(P＜0.01).PNH患者血浆suPAR水平与粒细胞表面uPAR的表达呈负相关(r=-0.79,P＜0.01).结论 PNH患者粒细胞表面uPAR表达水平降低,而血浆suPAR水平增高,这一变化可作为诊断PNH新的特异性指标.     

疏血通对急性心肌梗死患者尿激酶及其受体的影响

目的 观察疏血通对急性心肌梗死患者血浆尿激酶(u-PA)浓度及全血中性粒细胞表面尿激酶受体(u-PAR)表达率的影响.方法 选取2007年6月-2008年6月在我院确诊的急性心肌梗死患者84例,将患者随机分为治疗组和对照组,对照组采用常规治疗;治疗组在常规治疗的基础上加用疏血通,将疏血通4 mL加入生理盐水250 mL中静脉输注,每日1次,疗程为2周.检测两组患者的血浆尿激酶浓度及全血中性粒细胞表面尿激酶受体表达率.结果 治疗组治疗后血浆尿激酶浓度及中性粒细胞表面尿激酶受体表达水平较对照组下降,差异有统计学意义(P<0.05).结论 疏血通能够降低血浆尿激酶浓度及下调中性粒细胞表面尿激酶受体的表达,改善患者预后.     

血浆uPA系统与非小细胞肺癌相关性探讨

应用ELISA法检测78例非小细胞肺癌（NSCLC）患者治疗前后血浆尿激酶型纤溶酶原激活因子及其受体、抑制因子（uPA,uPAR,PAI-1）水平。结果NSCLC患者治疗前血浆uPA、uPAR和PAI．1水平均显著升高（P均〈0．001）,治疗后均下降。血浆uPA、uPAR、PAI．1水平与肿瘤大小、TNM分期及淋巴结转移相关;与病理类型及分化程度无关。血浆uPA、uPAR、PAI-1之间均呈直线相关。提示血浆uPA、uPAR和PAI-1可作为肿瘤标志物用于肺癌的诊断和病情观察。     

uPA和uPAR在老年急性髓系白血病中治疗前后表达的变化

目的 观察老年急性髓系白血病患者治疗前后骨髓单个核细胞尿激酶型纤溶酶原激活剂受体(uPAR)及血浆尿激酶型纤溶酶原激活剂(uPA)水平表达的变化.方法 应用流式细胞术及酶联免疫吸附试验检测60例老年急性髓细胞白血病患者(包括M1 4例,M2 15例,M3 13例,M4 15例,M5 13例)uPAR(CD87)及uPA表达情况,将治疗前患者定义为治疗前组,治疗后达完全缓解的患者定义为治疗后组,并分析两组表达的差异.结果 老年急性髓系白血病患者血浆中uPA水平和骨髓单个核细胞uPAR水平治疗前高于治疗后(P＜0.05);Pearson相关分析显示治疗前后uPA表达水平及uPAR水平之间存在正相关性(治疗前r1=0.874,治疗后r2=0.943;P ＜0.05).结论 老年急性髓细胞白血病治疗前uPAR(CD87)及uPA表达高于治疗后,并且二者具有协同表达关系,联合检测对于老年急性髓系白血病的病情监控有指导意义.     

可溶性尿激酶型纤溶酶原激活物受体在RA患者血浆和滑液的水平及其临床意义

目的检测可溶性尿激酶型纤溶酶原激活物受体(suPAR)在类风湿关节炎(RA)患者血浆和滑液中的含量,并结合临床资料和实验室指标分析其临床意义。方法采用酶联免疫吸附试验(ELISA)法分别检测了66例RA、23例骨关节炎(OA)和20名健康体检者的血浆,以及15例RA、9例OA患者滑液中suPAR的水平,比较不同病情活动组之间suPAR含量的变化,分析血浆和滑液中suPAR的含量与RA临床和实验室指标的相关性联系。同时观察其中16例RA患者治疗后血浆中suPAR的变化。结果RA患者血浆中suPAR的含量明显高于OA组和正常对照组(P均＜0．01),且血浆中suPAR水平随着RA病情活动程度的增强而增高。RA和OA滑液中suPAR水平均高于相应外周血水平(P＜0．01和P＜0．05),而RA滑液suPAR水平明显高于OA滑液(P＜0．01)。RA血浆和滑液中suPAR水平均与反映RA病情活动的指标如关节肿胀数、血沉(ESR)和C反应蛋白(CRP)呈正相关。治疗后RA患者血浆中suPAR水平明显下降(P＜0．05)。结论RA患者血浆和滑液中suPAR水平明显增高,提示其在RA病理过程中发挥重要作用,而且血浆suPAR水平与RA患者病情严重程度相关,可以作为判断RA病情活动的有效指标。     

多发性骨髓瘤患者血浆suPAR变化的临床意义

采用ELISA法检测38例多发性骨髓瘤（MM）患者及25例正常者（对照组）的血浆可溶性尿激酶型纤溶酶原激活剂受体（suPAR）水平及其他临床指标。结果与对照组比较,MM组suPAR明显升高（P〈0．01）,但各亚型间无统计学差异;suPAR水平与血沉、肌酐、Hb、临床分期相关。提示MM患者suPAR变化有助于判断病情及预后。     

肺癌患者血浆一氧化氮含量检测及临床意义

目的　探讨肺癌患者血浆一氧化氮浓度变化的临床意义。　方法　采用分光光度法对 4 8例肺癌患者进行了血浆一氧化氮含量检测。　结果　 4 8例肺癌患者与正常对照组血浆一氧化氮分别为 5 90 2 μmol L±1 15 7μmol L和 2 0 16 μmol L± 0 5 2 4 μmol L ,二者有显著差异 (P <0 0 5 )。　 结论　高水平一氧化氮与肺癌发生、发展有关。血浆一氧化氮高低对肺癌预后起一定作用。     

肾病综合征患者纤溶酶原激活物及其抑制物的变化及低分子肝素干预研究

肾小球硬化的病理生理基础是肾小球细胞外基质(ECM)积聚 ,纤溶酶原激活物及其抑制物 (PA/PAI)是调节ECM降解的重要酶系 ,研究表明肾炎病变组织中存在PA/PAI的异常表达[1] ,但在肾炎患者血浆中的变化报道甚少。本研究测定原发性肾病综合征 (NS)患者血浆组织型纤溶酶原激活物 (tPA)、尿激酶型纤溶酶原激活物 (uPA)、尿激酶型纤溶酶原激活物受体 (uPAR)、纤溶酶原激活物抑制物 1(PAI 1)的改变以及低分子肝素 (LMWH)干预治疗对上述指标的影响。1　对象和方法1.1　研究对象　选择本院 2 0 0 1- 0 4～ 2 0 0 3- 0 5确诊的原发性NS …     

Elevated soluble urokinase plasminogen activator receptor in plasma from patients with idiopathic myelofibrosis or polycythaemia vera

Extracellular proteolytic enzymes of the urokinase-type plasminogen activator (uPA) system and the family of metalloproteases play a crucial role in the matrix degradation and tissue remodelling processes characteristic of malignant disorders. The receptor for urokinase plasminogen activator (uPAR) serves to localise and intensify the action of uPA and is expressed on the surface of malignant as well as tumour stromal cells including fibroblasts. A soluble form of uPAR (suPAR) cleaved from its glycosyl-phosphatidylinositol anchor is detected in plasma from healthy individuals and increased levels of suPAR have been found in advanced malignancy, suggesting that suPAR may be a marker of extensive tissue remodelling. In an attempt to clarify whether suPAR might be a marker for bone marrow tissue remodelling we measured plasma suPAR levels in a patient cohort comprising 17 with myelofibrosis (MF), 17 with polycythaemia vera (PV), 15 with essential thrombocythaemia (ET), one with a transitional myeloproliferative disorder evolving from PV and 30 controls. Compared with controls suPAR levels were significantly higher in the patients (P < 0.0001) (median 3.35 vs. 2.32 microg L(-1)). Moreover, in subgroup analyses including patients with MF, PV, and ET, respectively, suPAR levels differed significantly with the highest levels found in patients with MF and PV (MF vs. PV vs. ET; P = 0.0003). When comparing suPAR levels of the individual patient subgroups with controls, only suPAR levels of PV and MF patients were significantly increased (P < 0.0001). Sixty-five percent of patients with PV and MF (22/34) had suPAR plasma values that were above the mean +2 standard deviations (SD) of controls. The concentration of suPAR was significantly correlated to plasma lactate dehydrogenase, thrombomodulin, and complex of tPA:PAI-1 in the patients. There was no difference between patients and controls when comparing plasma uPA levels. Increased plasma suPAR levels in patients with chronic myeloproliferative disorders may reflect increased uPAR production in the bone marrow, leading to enhanced bone marrow remodelling.     

Soluble urokinase plasminogen activator receptor (suPAR) for assessment of disease severity in ventilator-associated pneumonia and sepsis

Urokinase plasminogen activator (uPAR) is a receptor mainly expressed on peripheral blood mononuclear cells and neutrophils. The role of its soluble form, namely suPAR, as a predictor of sepsis outcome in a homogenous cohort of 180 septic patients, was investigated. Blood from 180 patients with ventilator-associated pneumonia (VAP) and sepsis was collected for seven consecutive days. suPAR and PCT were measured in serum by an enzyme immunoassay and an immuno-time-resolved amplified cryptate assay respectively. Neutrophils and monocytes were isolated on day 1 and incubated. suPAR levels greater than 10.5 ng/ml had 80% specificity and 77.6% positive predictive value to discriminate between severe sepsis and sepsis. suPAR levels greater than 12.9 ng/ml had 80% specificity and 76.1% positive predictive value for prognosis of unfavorable outcome. suPAR levels were significantly lower among survivors than among non-survivors over follow-up. Step-wise Cox regression analysis found suPAR as an independent factor related with unfavorable outcome (p: 0.026). Concentrations of suPAR in supernatants of neutrophils of patients with sepsis were greater compared to controls. It is concluded that suPAR is a reliable marker of sepsis severity and a strong independent predictor of unfavorable outcome in VAP and sepsis. Neutrophils are involved in release.     

Increased soluble urokinase plasminogen activator receptor (suPAR) is associated with thrombosis and inhibition of plasmin generation in paroxysmal nocturnal hemoglobinuria (PNH) patients

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired genetic disorder of the bone marrow that produces intravascular hemolysis, proclivity to venous thrombosis, and hematopoietic failure. Mutation in the PIG-A gene of a hematopoietic stem cell abrogates synthesis of glycosylphosphoinositol (GPI) anchors and expression of all GPI-anchored proteins on the surface of progeny erythrocytes, leukocytes, and platelets. Urokinase plasminogen activator receptor (uPAR), a GPI-linked protein expressed on neutrophils, mediates endogenous thrombolysis through a urokinase-dependent mechanism. Here we show that membrane GPI-anchored uPAR is decreased or absent on granulocytes and platelets of patients with PNH, while soluble uPAR (suPAR) levels are increased in patients' plasma. Serum suPAR concentrations correlated with the number of GPI-negative neutrophils and were highest in patients who later develop thrombosis. In vitro, suPAR is released from PNH hematopoietic cells and from platelets upon activation, suggesting that these cells are the probable source of plasma suPAR in the absence of GPI anchor synthesis and trafficking of uPAR to the cell membrane. In vitro, the addition of recombinant suPAR results in a dose-dependent decrease in the activity of single-chain urokinase. We hypothesized that suPAR, prevents the interaction of urokinase with membrane-anchored uPAR on residual normal cells.     

肺癌患者凝血常规指标检测的临床意义

目的探讨肺癌患者凝血功能相关指标与临床病理特征及预后的相关性。方法对60例肺癌患者及20例健康人的血浆凝血酶原时间（PT）、纤维蛋白原（FIB）、部分活化凝血活酶时间（APTT）分别进行测定。结果肺癌患者血浆纤维蛋白原水平显著高于健康对照组（P〈0.01）,血浆PT、APTT值与对照组相比无显著性差异。肺癌组中除PT值在性别上有显著性差异外（P〈0.05）,其余各指标与患者的年龄、性别、病理类型、肿瘤大小、TNM分期、有无远处转移等临床病理特征之间无明显关系。血浆纤维蛋白原与生存期之间有显著的负相关（r=-0.32,P〈0.01）。结论肺癌患者存在血浆纤维蛋白原水平增高,血浆纤维蛋白原水平与患者的生存期呈负相关,抗凝治疗对改善肺癌的预后可能有益。     

Urokinase plasminogen activator receptor and soluble matrix metalloproteinase-9 in acute myeloid leukemia patients: a possible relation to disease invasion

Extracellular proteolytic enzymes of the urokinase-type plasminogen activator (uPA) and metalloproteinase (MMP) family play a crucial role in the matrix degradation and tissue remodeling process characteristic of malignant disorders. The receptor for urokinase plasminogen activator (uPAR) serves to localize and intensify the action of UPA and is expressed on the surface of malignant cells. Although the biological significance of MMP-9 and soluble urokinase receptor in growth and progression of lymphoid neoplasm is understood, its clinical significance in acute myeloid leukemia (AML) has not been fully elucidated. In this study, we determined the levels of soluble urokinase-type plasminogen activator receptor (suPAR), cellular uPAR and sMMP-9 in 43 newly diagnosed AML patients at diagnosis, before chemotherapy, and also studied 10 normal subjects served as a control group. After chemotherapy suPAR and MMP-9 were determined at remission and relapse. The levels of suPAR, cellular PAR were significantly higher (P= 0.001, 0.001) and MMP-9 was significantly lower (P=0.001) in AML patients at diagnosis as compared to controls. suPAR and MMP-9 levels were significantly lower in AML patients who achieved complete remission (CR) as compared to those who did not (P= 0.001 for both). Levels of suPAR and MMP-9 were significantly correlated to peripheral blood blast cells (r= 0.88, P= 0.001; r= 0.65, P= 0.001, respectively) and blast cell distribution ratio (BCDR, r= 0.84, P= 0.001; r=65, P= 0.001, respectively). suPAR, cellular PAR and MMP-9 were significantly higher in patients with extramedullary infiltration as compared with those without (P= 0.001, 0.001, <0.05). The suPAR, cellular uPAR, and MMP-9 levels were uneven in AML FAB subtypes being highest in M5(P<0.05 for all). MMP-9 and suPAR levels were correlated with the disease status. In AML survivors, MMP-9, cellular uPAR and suPAR were significantly lower as compared to non-survivors (P= 0.001 for all). In conclusion, MMP-9 and su PAR levels might be used as a marker for disease activity and may contribute to blast cell dissemination. MMP-9 and suPAR may be target molecules in the strategy of treatment of AML.     

Soluble urokinase-type plasminogen activator receptor (suPAR) as an independent factor predicting worse prognosis and extra-bone marrow involvement in multiple myeloma patients

The urokinase-type plasminogen activator (uPA) system, which consists of a proteinase (uPA), a receptor (uPAR or CD87) and inhibitors, is involved in proteolysis, cell migration, tissue remodelling, angiogenesis and cell adhesion. Recent findings suggest that malignant plasma cells express uPA and uPAR. The expression of these factors could represent a process by which myeloma plasma cells interact with the bone marrow (BM) environment and influence important biological events such as bone matrix degradation, plasma cell invasion and homing and, possibly, clinical evolution. We evaluated uPAR (CD87) and its soluble form (suPAR) in 49 multiple myeloma (MM) patients and correlated their expression and levels with clinico-biological characteristics of the disease. Flow cytometric analysis demonstrated that CD87 was expressed in all MM patients. High CD87 expression was associated with higher intensity of expression of CD56 (P = 0.038), CD38 (P = 0.058) and CD138 (P = 0.054) and CD45bright positivity (P = 0.014). suPAR levels correlated positively with soluble serum CD138 (P = 0.001), creatinine (P = 0.001), beta2-microglobulin (P < 0.001), disease stage (P = 0.017) and extra-BM involvement (P = 0.002). In the 46 evaluable patients, multivariate analysis showed that high levels of suPAR (P = 0.0214) and disease stage (P = 0.0064) were predictive of extra-BM involvement. In multivariate Cox analysis, 13q deletion (P = 0.0278), high soluble serum CD138 (P = 0.0201) and high suPAR (P = 0.0229) were the only parameters that independently affected survival. We conclude that CD87 is expressed on myeloma plasma cells and that suPAR, which predicts extra-BM involvement and poor prognosis, possibly represents a molecule with a relevant role in the biology of MM.     

Diagnostic significance of measurement of the receptor for urokinase-type plasminogen activator on granulocytes and in plasma from patients with paroxysmal nocturnal hemoglobinuria

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired stem cell disorder characterized by the deficiency of all proteins anchored to the membrane by the glycosyl-phosphatidylinositol (GPI) anchor. The receptor for urokinase-type plasminogen activator (uPAR) also is attached to the cell membrane by a GPI anchor, and that soluble uPAR (suPAR) is present in plasma. In the present study, we measured uPAR, CD55, and CD59 on granulocytes by means of flow cytometry and suPAR in plasma by means of immunoradiometric assay. The subjects were 20 patients with PNH, 59 other patients with anemia, and 21 healthy individuals. In patients with PNH, both the mean fluorescence intensity and the positive percentage of fluorescence-activated granulocytes of uPAR, CD55, and CD59 were remarkably decreased, whereas in patients with other forms of anemia, except 2 patients with aplastic anemia, the results were not altered in comparison with those for the healthy individuals. The level of uPAR was reduced to the same extent as were those of CD55 and CD59 on the PNH-affected granulocytes. Some peak shape abnormalities (double peaks, peak tailing, or both) in the histogram of fluorescence intensity were also found in patients with PNH. The suPAR concentration of PNH plasma was 4.04+/-2.47 ng/mL, which was higher than that of the healthy individuals, 1.73+/-0.96 ng/mL (P < .01). The positive percentage of fluorescence-activated granulocytes was inversely associated with the plasma suPAR level in patients with PNH (r = -0.79, P < .01). Our data suggest that measurement of uPAR on granulocytes by means of flow cytometry and of suPAR in plasma by means of immunoradiometric assay are specific techniques for the diagnosis of PNH.     

晚期肺癌患者D-二聚体水平及其临床意义

目的探讨晚期肺癌患者D-二聚体水平及临床意义。方法选取我院2010年1月~2014年1月收治110例晚期肺癌患者作为观察对象,设为晚期肺癌组,选取同期110例健康体检者,设为健康对照组,检测两组的血浆D-二聚体水平,同时比较晚期肺癌不同分期、不同病理类型、有无转移与D-二聚体水平之间的关系,比较血浆D-二聚体阳性及阴性患者化疗后的中位无进展生存期(PFS)。结果晚期肺癌患者的血浆D-二聚体水平明显高于健康对照组(P0.01);晚期肺癌Ⅳ期患者的D-二聚体水平明显高于ⅢB期患者(P0.01);不同病理类型肺癌患者的D-二聚体水平比较无统计学差异(P0.05);晚期肺癌转移患者的D-二聚体水平显著高于未发生转移的患者(P0.01);血浆D-二聚体表达阳性的患者的中位PFS明显短于阴性患者(P0.01)。结论晚期肺癌患者血浆D-二聚体水平与肿瘤分期、转移与否密切相关,血浆D-二聚体水平阳性的患者PFS更短,故可作为晚期肺癌预后判断的重要指标。