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1.
Relationships between Activators and Inhibitors of Plasminogen, and the Progression of Small Abdominal Aortic Aneurysms 总被引:1,自引:0,他引:1
J. S. Lindholt B. Jrgensen G. -P. Shi E. W. Henneberg 《European journal of vascular and endovascular surgery》2003,25(6):546-551
OBJECTIVE: plasmin is a common activator of the known proteolytic systems involved in the aneurysmal degradation, and is reported to be associated with the expansion of abdominal aortic aneurysms (AAA). The aim of this study was to study the activating pathways of plasminogen as predictors of the progression of AAA. MATERIALS AND METHODS: one hundred and twelve of 122 male patients with a small AAA (def.: +3cm) were interviewed, examined, had blood samples taken at diagnosis, and scanned annually for 1-5 years (mean 3.5 years), and referred for surgery if the AAA exceeded 5cm in diameter.A random sample of 70 of the 112 cases had plasma levels of urokinase-like-plasminogen activator (uPA), tissue-type-plasminogen activator (tPA), plasminogen-activator-inhibitor-1 (PAI-1), macrophage inhibiting factor (MIF), tumour-growth-factor-beta1 (TGF-beta1), homocysteine, and serum levels of IgA-antibodies against Chlamydia pneumoniae (IgA-CP) and Cotinine (a nicotine metabolite) measured. Spearmans correlation analysis was used for statistics. RESULTS: the annual expansion rate correlated positively with tPA, IgA-CP and S-Cotinine; r =0.37 (p=0.002), 0.29 (p=0.006) and 0.24 (p=0.038), while PAI1, uPA, TGF-beta1, homocysteine, and MIF did not. S-Cotinine did also correlate positively with tPA, r=0.24 (p=0.049). CONCLUSION: the aortic matrix degradation in AAA may be partly caused by an activation of plasminogen by tPA, but apparently not by uPA, which usually dominates matrix degradation. Smoking seems to be a factor for this pathway, while the pathways of IgA-CP and MIF, a new marker of aneurysmal progression, seem different. The latter observations suggest that other proteolytic pathways are involved in the aortic wall degradation in AAA. 相似文献
2.
Growth factor-dependent activation of the MAPK pathway in human pancreatic cancer: MEK/ERK and p38 MAP kinase interaction in uPA synthesis 总被引:3,自引:0,他引:3
Increased expression of the hepatocyte growth factor (HGF) receptor (c-met) and urokinase type plasminogen (uPA) correlated
with the development and metastasis of cancers. To investigate the role of HGF/c-met signaling on metastasis in cancer cells
stimulated with HGF, we examined the effects of a specific MEK1 inhibitor (PD98059) and a p38 MAP kinase inhibitor (SB203580)
on HGF-induced uPA expression in pancreatic cancer cell lines, L3.6PL and IMIM-PC2. Pretreatment of PD98059 decreased HGF-mediated
phosphorylation of extracellular receptor kinase (ERK), uPA secretion and expression of matrix metalloproteinases (MMP-2 and
MMP-9) in a dose-dependent manner. In contrast, SB203580 pretreatment increased HGF-stimulated ERK phosphorylation, uPA secretion
and expression of MMPs. SB203580 also reversed the inhibition of HGF-mediated ERK activation and uPA secretion in the PD98059-pretreated
cells. These results suggest that ERK activation by HGF might play important roles in the metastasis of pancreatic cancer
and the p38 MAPK pathway also involved in the HGF-mediated uPA secretion and metastasis by regulation of ERK pathway.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
3.
Brooks TD Slomp J Quax PH De Bart AC Spencer MT Verheijen JH Charlton PA 《Clinical & experimental metastasis》2000,18(6):445-453
Recent reports suggest that elevated levels of plasminogen activator inhibitor-1 (PAI-1) may contribute to tumour progression.
The studies reported here were designed to help elucidate PAI-1's contribution to the invasive and migratory phenotype. Antibodies
to PAI-1 dose-dependently, and significantly, inhibited the invasive and migratory potential of human HT1080 fibrosarcoma
cells, as did an antibody to uPA and the plasmin inhibitor aprotinin. Invasion of the human melanoma cell line, BLM, was also
attenuated by the anti-PAI-1 monoclonal antibody MAI-12. The non-invasive human melanoma cell line, IF6, which does not express
uPA, provided further confirmation of PAI-1 and uPA's role as, upon transfection with uPA, this cell line attained an invasive
phenotype, which was again attenuated by MAI- 12. Although antibodies to PAI-1 did not affect the adhesion of HT1080 cells
to vitronectin, the antibody to uPA reduced their attachment. Addition of exogenous PAI-1, however, prevented HT1080 cell
adhesion (IC50 180nM) and promoted cell detachment from vitronectin. Furthermore melanoma cells transfected with a uPA variant, which had
an impaired interaction with PAI-1, were not invasive and had impaired binding to vitronectin. These data highlight the importance
of a balanced proteolysis and suggest an additional role for PAI-1 distinct from its role in proteolysis. These data also
suggest that uPA and PAI-1 may co-operate in the migratory process by respectively facilitating the attachment to, and subsequent
detachment from, vitronectin in the extracellular matrix. These results support the clinical findings and indicate that modulation
of PAI-1 activity may be of therapeutic benefit for the treatment of cancer.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
4.
检测切应力作用下肾近端小管上皮细胞纤溶酶原激活物tPA和uPA mRNA表达的变化,探讨糖尿病肾病早期小管间质细胞外基质重塑的可能机制.用5 dyn/cm2和10 dyn/cm2的切应力处理肾近端小管上皮细胞(NRK-52E),作用时间分别为1、3和6 h,用RT-PCR法检测tPA及uPA mRNA的表达.结果表明:切应力呈大小和时间依赖性下调肾小管上皮细胞tPA及uPA mRNA的表达.在糖尿病肾病早期,高滤过引起的切应力增加可抑制肾近端小管上皮细胞tPA和uPA mRNA表达,导致肾小管间质纤维蛋白溶解活性降低,参与小管间质细胞外基质的重塑. 相似文献
5.
目的 制备抗人尿激酶受体单克隆抗体,为今后uPAR 病理生理作用及临床意义的研究提供新的手段。方法 利用杂交瘤技术,用经PMA刺激的U937 细胞与可溶性尿激酶受体(suPAR)免疫Balb/c 小鼠,与SP2/0 细胞融合。结果 获得国内第1 组4 株抗人尿激酶受体(uPAR)单抗,分别命名为SZ- 98、SZ- 99 、SZ- 100 、SZ- 101。结论 4 株单抗均能与uPAR 特异性结合,能与U937 细胞及经PMA作用的K562 细胞反应。SZ- 101 与国外抗uPAR单抗3936 有相同的uPAR 结合位点;而SZ-98、SZ- 99 与SZ- 100 在uPAR上有不同的结合位点 相似文献
6.
目的探讨尿激酶型纤溶酶原激活剂(uPA)、尿激酶型纤溶酶原激活剂受体(uPAR)和nm23H1基因蛋白在大肠癌中的表达及其与肿瘤侵袭和淋巴结转移的关系。方法应用免疫组化SABC法,对121例大肠癌手术根治标本进行uPA、uPAR和nm23H1基因蛋白测定。结果uPA、uPAR和nm23H1阳性表达率分别为62%、74%和48%。uPA和uPAR高表达与大肠癌侵袭和淋巴结转移关系密切(P<0.05)。nm23H1基因蛋白的低表达与大肠癌分化程度和淋巴结转移密切相关(P<0.05)。大肠癌中uPA和nm23H1蛋白表达呈负相关(P<0.05)。结论uPA、uPAR和nm23H1基因蛋白表达与大肠癌侵袭和转移有显著相关性;同时检测uPA和nm23H1表达状况,可作为预测大肠癌淋巴结转移及预后的有用指标。 相似文献
7.
目的:在人乳腺癌模型上研究双调蛋白与尿激酶型纤溶酶原活化物表达之间的关系.方法:乳腺癌NS2T2A1细胞经双调蛋白反义cDNA质粒转染后经潮霉素B筛选获得表达双调蛋白反义RNA的AR-AS1及AR-AS3两个细胞克隆,转染空载体获得NS2T2A1 V对照细胞,接种至裸鼠皮下形成肿瘤.测定细胞及肿瘤uPA表达水平,并研究uPA与细胞侵袭性之间的关系.结果:AR-AS1及AR-AS3细胞体外及体内uPA表达均被抑制.外源性双调蛋白可刺激对照细胞uPA的表达,并部分恢复AR-AS1及AR-AS3细胞uPA的表达水平.双调蛋白反义cDNA质粒转染及抗uPA抗体均导致乳腺癌细胞体外侵袭性的降低.结论:在乳腺癌模型上,uPA表达与肿瘤细胞的侵袭密切相关.双调蛋白反义RNA表达可有效地抑制uPA的表达,进而抑制肿瘤细胞的侵袭性. 相似文献
8.
目的 探讨尿胰蛋白酶抑制剂(U TI) 在动物模型上抗肿瘤作用。方法 选用尿胰蛋白酶抑制剂乌司他丁(Ulinastatin) , Lewis 肺癌小鼠模型;雄性C57BL/ 6 小鼠40 只,接种lewis 肿瘤细胞,分成生理盐水组(对照组) 、环磷酰胺组(CTX) 、Ulinastatin 2. 5万单位组、Ulinastatin 5 万单位组、Ulinastatin 10万单位组,各8 只,接种后第6 天,开始腹腔给药,记录皮下瘤长短径变化,做生长曲线;接种14 天后处死所有小鼠,统计皮下平均瘤重和肺转移灶个数, 使用流式细胞计分析凋亡率(AR) 增值百分比(SPF) 。结果 皮下瘤重依次为(7. 92 ±2. 52 、0. 66 ±0. 50** 、3. 47 ±1. 45* 、3. 08 ±0. 81**、1. 70 ±1. 05**) g ,平均肺转移灶依次为( 8. 625 ±1. 407 、1. 125 ±1. 126**、1. 625 ±1. 302** 、1. 00 ±0. 75** 、0. 625 ±0. 74**) 。CTX 组(39. 3 ±4. 8) %* 和Ulinastatin 10 万单位组(40. 2 ±3. 1) %*的AR 值明显增加,Ulinastatin 未见SPF 值明显减少。结论 Ulinastatin 对lewis 肺癌小鼠的转移瘤生长和自发性肺转移有抑制作用。 相似文献
9.
目的:探讨尿激酶型纤溶酶原激活物(uPA)及其受体(uPAR)和抑制剂(PAI-1)血浆含量与卵巢恶性肿瘤之间的关系。方法:收集52例卵巢恶性肿瘤患者血液标本,以30例健康人作对照,用ELISA法分别检测uPA、uPAR和PAI-1的含量。结果:uPA、uPAR在卵巢恶性肿瘤各期之间均有极显著性差异(P〈0.01),PAI-1在卵巢恶性肿瘤FIGO Ⅰ~Ⅲ期的含量逐渐升高,但在FIG0Ⅳ期时显著下降(P〈0.05)。患者组uPA、uPAR、PAI-1均较对照组升高,差异极显著(P〈0.01)。结论uPA、uPAR在卵巢恶性肿瘤患者可作为预后的判断指标,PAI-1与卵巢恶性肿瘤的分期有一定的相关性。 相似文献
10.
目的研究膀胱移行细胞癌uPA、uPAR及抑癌基因PTEN蛋白的表达及其与肿瘤侵袭、转移的关系。方法应用免疫组织化学SP法检测60例膀胱移行细胞癌组织uPA、uPAR和PTEN蛋白的表达。结果uPA、uPAR和PTEN阳性表达率分别为50.00%、50.00%和41.67%。uPA和uPAR的高表达与膀胱移行细胞癌的分化程度、浸润和转移关系密切(P<0.05);PTEN蛋白的低表达与膀胱移行细胞癌的分化程度、浸润和转移密切相关(P<0.05);膀胱癌中uPA和uP-AR与PTEN蛋白表达呈负相关(r=-0.481,P<0.05)。结论uPA和uPAR的高表达可能作为膀胱移行细胞癌侵袭、转移的指征之一,PTEN可能作为膀胱移行细胞癌预后不良的指标;uPA和uPAR对肿瘤细胞侵袭转移的作用可能在一定程度上受到PTEN的调控。 相似文献