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.     

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。     

MMP-7与Fas蛋白在胃癌组织中的表达及意义

目的:探讨基质金属蛋白酶-7(MMP-7)蛋白和Fas蛋白在胃癌组织中的表达、相互关系及意义.方法:应用免疫组化方法检测了82例胃癌组织及30例周边正常胃黏膜中MMP-7和Fas的表达情况.结果:胃癌组织中MMP-7蛋白阳性率显著高于正常胃黏膜(73.2%vs10%,P<0.001);正常胃黏膜中Fas蛋白阳性率显著高于胃癌组织(39.1%vs93.3%,P<0.001).MMP-7阳性表达率与淋巴结转移、TNM分期显著相关(P<0.001),而与肿瘤细胞分化程度无显著性相关.Fas蛋白阳性表达率与肿瘤细胞分化程度显著相关(P<0.05),而与淋巴结转移、TNM分期无显著性相关.胃癌组织中MMP-7与Fas表达具有显著等级负相关(r=-0.597,P<0.001).结论:MMP-7与Fas表达胃癌的生物学行为密切相关,且两者之间的表达强度具有显著等级负相关.     

OA患者血液及关节液中MMP-3、uPA水平检测及临床意义

目的 探讨基质金属蛋白酶-3（MMP-3）及尿激酶型纤溶酶原激活物（uPA）在膝关节骨关节炎（OA）发生、发展中的作用,为临床诊断及预后判定提供依据。方法 研究对象为308例膝关节OA患者（OA组）和36例健康体检者（对照组）,分别均抽取两组静脉血和膝关节液,用双抗体夹心ELISA法测定MMP-3与uPA水平,并分析各指标间及与病变程度的关系。结果 OA组血液及关节液中MMP-3、uPA均显著高于对照组（P〈0．001）;血液与关节液中MMP-3、uPA均分别呈线性正相关（P〈0．001）,r=0．69、0．71;MMP-3水平与病变程度呈正相关（P〈0．001）,r=0．86,但uPA水平与之无明显相关性。结论MMP-3、uPA均与OA患者发病相关,其中MMP-3与病变程度呈正相关,可作为OA临床辅助诊断和病情判定的标志物。     

MMP-7和E-cad在胃癌组织中表达的临床价值

目的 探讨基质金属蛋白酶-7(MMP-7)及上皮型黏附素(E-cad)在胃癌中的表达,关注二者在胃癌发生发展及转移中的作用.方法 收集我院105例胃癌术后存档的标本作为研究对象,34例正常胃黏膜组织作为对照组,应用免疫组织化学技术检测两组中MMP-7和E-cad的表达.结果 胃癌组织中MMP-7表达阳性率为74.29%,明显高于正常胃组织,胃癌组织中E-cad表达阳性率为33.33%,明显低于正常胃组织,MMP-7和E-cad在胃癌中的表达均与浸润及淋巴结转移有关,胃癌中MMP-7和E-cad表达具有负相关性.结论 胃癌中MMP-7和E-cad异常表达,二者在胃癌癌变及进展中可能具有一定作用,术后联合检测MMP-7和E-cad可能对判断胃癌预后有一定价值.     

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。     

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。     

MMP-2、MMP-7与胃癌的侵袭转移关系探讨

目的　观察基质金属蛋白酶 (MMP)系列中的 型胶原酶 (MMP- 2 )和基质溶解素 (MMP- 7)在胃癌和癌旁组织中的表达 ,探讨其与胃癌侵袭转移的关系。方法　采用逆转录 - PCR(RT- PCR)方法分别检测 4 0例胃癌及癌旁组织 MMP- 2和 MMP- 7m RNA的阳性表达及含量。结果　 4 0例胃癌组织中 MMP- 2和 MMP- 7的阳性表达率分别为 82 .5 %、72 .5 % ,明显高于癌旁组织的 72 .5 %、17.5 % ,二者比较差异有显著性 (P<0 .0 0 1)。MMP-2和 MMP- 7表达量高于其癌旁组织 (t=3.6 7,t=7.894 ) ,差异有显著性 (P均≤ 0 .0 0 1)。MMP- 2和 MMP- 7的表达量与胃癌患者的性别、年龄、肿瘤的大小均无相关性 (P>0 .0 5 )。 MMP- 2的表达量在晚期、低分化及伴有淋巴结转移的胃癌患者中明显高于早期、高分化及无淋巴结转移的胃癌患者 (P<0 .0 5、P<0 .0 1)。 MMP- 7在各期胃癌中的表达无差异 (P>0 .0 5 ) ,但在中低分化及合并有淋巴结转移的胃癌患者中其表达量明显高于高分化及不伴有淋巴结转移的胃癌患者 (P<0 .0 5 )。结论　 MMP- 2和 MMP- 7的表达与胃癌侵袭转移性有关     

Relationship between matrix metalloproteinase-2 mRNA expression and clinicopathological and urokinase-type plasminogen activator system parameters and prognosis in human gastric cancer

AIM: To investigate the relationship between matrix metalloproteinase-2 (MMP-2) mRNA expression and clinicopathologic and urokinase-type plasminogen activator (uPA) system parameter and prognosis in human gastric cancer. METHODS: Expression of MMP-2 mRNA, uPA, and uPA-R mRNA in tumor tissues and ≥5 cm adjacent normal tissues from 67 cases of gastric cancer was studied using RT-PCR and Northern blot respectively.Survival analyses were done using the Kaplan-Meier method. RESULTS: The expression rates of MMP-2 mRNA,uPA and uPA-R mRNA in tumor tissues (31%,41%,and 51%, respectively) were significantly higher than those in ≥5 cm adjacent tissues (19%, 11%, and 9%; X2=4.59,43.58, and 53.24 respectively, P<0.05,0.0001,and 0.0001, respectively). Expression of MMP-2 mRNA was significantly correlated with lymph node metastasis (metastasis: 61.9%, no metastasis: 39.1%, X2= 7.61, P<0.05),Lauren's classification of diffuse/mixed types:54.2%,intestinal type: 26.3%,X2 = 4.25, P<0.05, expression of uPA and uPA-R mRNA (uPA+: 55.1%, uPA-: 22.2% and uPA-R+: 54.9%, uPA-R-: 18.8%, X2=5.72 and 6.40 respectively, P<0.05).Kaplan-Meier survival analysis of MMP-2 mRNA expression did not show significant difference in all 67 cases, but revealed an association of the expression of MMP-2 mRNA, uPA, and uPA-R mRNA with worse prognosis (P= 0.0083, 0.0160, and 0.0094, respectively). CONCLUSION: MMP-2 may play an important role in the development of invasion and metastasis of gastric cancer.     

胃癌VEGF-D、MMP-2的表达与淋巴结转移的关系

目的检测血管内皮生长因子D（vascular endothelial growth factor-D,VEGF-D）、基质金属蛋白酶-2（matrix metalloprotein-ase-2,MMP-2）在胃癌中的表达情况,探讨它们在胃癌发生淋巴结转移中的作用和意义。方法应用免疫组化SABC法检测VEGF-D、MMP-2在正常胃黏膜及胃癌组织中的表达情况。结果VEGF-D在正常胃黏膜中阴性表达,在胃癌组织中阳性表达率为41.3%（P〈0.01）,MMP-2在正常胃黏膜细胞中阳性表达率为15%,在胃癌组织中的阳性表达率为54.0%（P〈0.01）。VEGF-D阳性表达率在有淋巴结转移组为61.3%,显著高于无淋巴结转移组（21.9%）,MMP-2阳性表达率在有淋巴结转移组（77.4%）显著高于无淋巴结转移组（31.3%）。此外,VEGF-D、MMP-2的阳性表达与胃癌的组织学分级、浸润深度密切相关,VEGF-D的阳性表达与MMP-2的阳性表达密切相关。结论VEGF-D、MMP-2在胃癌中的过表达可能参与了胃癌的淋巴道转移,VEGF-D可能通过增强MMP-2的表达,提高肿瘤细胞的侵袭性和转移能力。     

血管生成素-2与基质金属蛋白酶-7在大肠癌中的表达及意义

目的:研究血管生成素-2(Ang-2)及基质金属蛋白酶-7(MMP-7)蛋白在人大肠癌组织中的表达及其与大肠癌临床病理特征的关系．方法:应用免疫组化法检测40例大肠癌及其癌旁正常组织中Ang-2及MMP-7蛋白表达水平．结果:大肠癌组织中Ang-2蛋白表达阳性率为77．5％(31/40),明显高于癌旁正常组织 40％(16/40)(P=0．001);Ang-2表达水平与患者性别、年龄及癌组织的部位、大小、分化程度、淋巴结转移无关(P>0．05);与浸润深度, 远处转移及Dukes’分期相关(分别为P=0．007, P=0．023,P=0．008);大肠癌组织RMMP-7蛋白表达阳性率为85％(34/40),明显高于癌旁正常组织35％(14/40)(P=0．000)．MMP-7蛋白表达阳性率与Ang-2的表达相关(P=0．016)．结论:Ang-2蛋白可能通过促进MMP-7的表达从而促进了大肠癌的生长及转移．     

Autoantibodies against MMP-7 as a novel diagnostic biomarker in esophageal squamous cell carcinoma

AIM: To evaluate the diagnostic values of serum autoantibodies against matrix metalloproteinase-7 (MMP-7) in patients with esophageal squamous cell carcinoma (ESCC). METHODS: The MMP-7 cDNA was cloned from ESCC tissues, and MMP-7 was expressed and purified from a prokaryotic system. MMP-7 autoantibodies were then measured in sera from 50 patients with primary ESCC and 58 risk-matched controls, using a reverse capture enzyme-linked immunosorbent assay (ELISA) in which autoantibodies to MMP-7 bound to the pur...     

巨噬细胞抑制因子-1及尿激酶型纤容酶原激活剂在胃癌组织中的表达及临床病理意义

目的:探讨巨噬细胞抑制因子-1(macrophage inhibitory cytokine-1,MIC-1)及尿激酶型纤容酶原激活剂(urokinase plasminogen activator,uPA)在胃癌组织中的蛋白表达及其临床意义.方法:收集郑州大学第一附属医院2009-01/2010-05胃癌存档蜡块55...     

Increased expression of MMP-2 and MMP-9 in esophageal squamous cell carcinoma.

Purpose Matrix metalloproteinases (MMPs) are known to play an important role in extracellular matrix remodeling during the process of tumor invasion and metastasis. However, little is known about their role in preinvasive lesions and early esophageal carcinomas.Method Immunohistochemical analysis of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) expression was carried out in paraffin-embedded sections of surgically resected esophageal squamous cell carcinoma (ESCC) (58 cases) and paired distal normal esophageal tissues (44 cases) and correlated with clinicopathological parameters.Result Overexpression of MMP-2 and MMP-9 proteins was observed in 39 (67%) and 32 (55%) of the 58 ESCCs, respectively localized in tumor cell cytoplasm and stromal elements. Histological evaluation of hematoxylin- and eosin-stained 44 matched distal normal esophageal tissue sections revealed that 26 comprised of normal epithelium, while 15 tissues showed evidence of dysplasia and three tissues showed hyperplasia. Interestingly, 12 (80%) and 13 (87%) of these 15 dysplasias showed immunostaining for MMP-2 and MMP-9 proteins, respectively. Low levels of MMP-2 and MMP-9 were observed in 10 (38%) and 6 (23%) of 26 matched histologically normal esophageal tissues, respectively. Higher MMP-2 immunopositivity was observed in well and moderately differentiated SCCs in comparison with poorly differentiated tumors. The expression of MMP-2 was significantly reduced with the progressive de-differentiation of esophageal SCCs (P =0.03). Overexpression of MMP-2 and MMP-9 in dysplasia as well as SCC suggests that these alterations occur in early stages of esophageal tumorigenesis.Conclusion Increased levels of MMP-2 and MMP-9 proteins in ESCCs as compared to normal esophageal tissues suggest their association with esophageal tumorigenesis. Increased levels of these MMPs are observed in majority of dysplasias analyzed herein, indicating that these alterations may be early events in esophageal tumorigenesis. In-depth studies are warranted to determine their role in development and progression of esophageal cancer.     

胃癌组织MMP-9基因与血清中蛋白相关性研究

目的了解胃癌组织中基质金属蛋白酶-9（MMP-9）基因表达与术前血清中蛋白水平关系，探讨MMP-9表达与胃癌临床病理参数之间相关性。方法45例胃癌组织通过半定量逆转录聚合酶链反应（semi-RT-PCR）、免疫组织化学染色（IHC）、酶联免疫吸附（ELISA）方法检测组织中mRNA及蛋白表达情况，测定术前血清中蛋白水平。结果肿瘤组织基质金属蛋白酶-9mRNA表达程度、蛋白染色阳性率、血清中蛋白水平均显著高于正常对照组（P〈0．01）；胃癌组织蛋白表达阳性率与肿瘤是否侵犯至浆膜层相关（P〈0．05）；术前血清中蛋白水平与肿瘤TNM分期、淋巴结转移显著相关（P〈0．01）。结论检测基质金属蛋白酶-9表达对胃癌有一定诊断意义；胃癌组织中蛋白表达率及术前血清中蛋白水平对临床肿瘤病情评估具有指导意义；也许多种机制参与了胃癌术前血清中MMP-9蛋白的分泌。     

Correlative studies on uPA mRNA and uPAR mRNA expression with vascular endothelial growth factor, microvessel density, progression and survival time of patients with gastric cancer

AIM: TO investigate the correlations between the expression of urokinase-type plasminogen activator (uPA) mRNA, uPA receptor (uPAR) mRNA and vascular endothelial growth factor (VEGF) protein and clinicopathologic features, microvessel density (MVD) and survival time. METHODS: In situ hybridization and immuno-histochemistry techniques were used to study the expressions of uPA mRNA, uPAR mRNA, VEGF and CD34 protein in 105 gastric carcinoma specimens. RESULTS: Expressions of uPA mRNA, uPAR mRNA and VEGF protein were observed in 61 (58.1%) cases, 70 (66.7%) cases and 67 (63.8%) cases, respectively. The uPA mRNA and uPAR mRNA positive expression rates in infiltrating-type cases (73.7%, 75.4%), stageⅢ-Ⅳ(72.1%, 75.4%), vessel invasion (63.2%, 69.9%), lymphatic metastasis (67.1%, 74.4%) and distant metastasis (88.1%, 85.7%) were significantly higher than those of the expanding-type (X2= 15.57, P= 0.001; X2=6.91, P=0.046), stageⅠ-Ⅱ(X2 = 19.22, P = 0.001; X2= 16.75, P= 0.001), non-vessel invasion (X2 = 11.92, P = 0.006; X2 = 14.15, P = 0.002), non-lymphatic metastasis (X2 = 28.41, P = 0.001; X2= 22.5, P=0.005) and non-distant metastasis (X2 = 12.32, P= 0.004; X2= 17.42, P = 0.002; X2 = 11.25, P = 0.012; X2 = 18.12, P = 0.002).The VEGF positive expression rates in infiltrating-type cases (75.4%), stageⅢ-Ⅳ(88.5%), vessel invasion (82.9%), lymphatic metastasis (84.3%) and distant metastasis (95.2%) were significantly higher than those of the expanding-type (X2 = 9.61, P = 0.021), stage I-II (X2=16.66, P = 0.001), non-vessel invasion (X2= 29.38, P = 0.001), non-lymphatic metastasis (X2 = 18.68, P = 0.005), and non-distant metastasis (X2= 22.72, P = 0.007; X2 = 21.62, P = 0.004). The mean MVD in the specimens positive for the uPA mRNA, uPAR mRNA and VEGF protein was markedly higher than those with negative expression groups. Moreover, a positive relation between MVD and uPA mRNA (rs = 0.199, P = 0.042), uPAR mRNA (rs = 0.278, P = 0.035), and VEGF (rs = 0.398, P = 0.048) expressions was observed. The mean survival time in cases with positive uPA mRNA, uPAR mRNA and VEGF protein expression or MVD value≥54.9 was significantly shorter than those in cases with negative expression or MVD value < 54.9. CONCLUSION: uPA and uPAR expressions are correlated with enhanced VEGF-induced tumor angiogenesis and may play a role in invasion and nodal metastasis of gastric carcinoma, thereby serving as prognostic markers of gastric cancer.     

Smad7反义寡核苷酸对人胰腺癌SW1990细胞MMP-2和TIMP-2表达及细胞增殖的影响

目的 研究Smad7反义寡核苷酸(ASODN)转染后人胰腺癌SW1990细胞基质金属蛋白酶-2(M MP-2)和基质金属蛋白酶组织抑制因子-2(TIMP-2)表达及细胞增殖的变化,探讨Smad7在胰腺癌发生、发展中的作用机制.方法 经脂质体介导将Smad7 ASODN转染人胰腺癌细胞株SW1990.以无义寡核苷酸( NSODN)转染、单加ASODN、单加脂质体作为对照.荧光显微镜及流式细胞仪检测转染效率;RT-PCR、蛋白质印迹法检测转染细胞Smad7、MMP-2和TIMP-2表达;噻唑蓝(MTT)比色法检测转染细胞的增殖.结果 Smad7 ASODN转染SW1990细胞的转染效率为81.2％,转染24h后,转染组、ASODN组和脂质体组细胞Smad7 mRNA表达量分别为0.34±0.06、0.95 ±0.07、1.03 ±0.11;MMP-2mRNA表达量为0.54 ±0.08、1.15 ±0.13、1.27 ±0.16;TIMP-2 mRNA表达量为0.26±0.07、0.72±0.13、0.78±0.17;Smad7蛋白表达量为0.14±0.03、0.29 ±0.05、0.28±0.07;MMP-2蛋白表达量为0.17±0.02、0.29±0.05、0.31±0.04;TIMP-2蛋白表达量为0.20±0.03、0.41±0.11、0.43±0.09.转染组均较其他各组的表达显著减少(P值均＜0.01).转染组、ASODN组、脂质体组细胞的增殖活性分别为0.83 ±0.03、1.02±0.02、0.99±0.02,转染组细胞的增殖活性较其他各组显著被抑制(P值均＜0.01).结论 Smad7 ASODN转染可有效抑制SW1990细胞Smad7基因的表达,并抑制MMP-2、TIMP-2表达及细胞增殖活性.     

Maspin在大肠腺瘤癌变过程中的表达及其意义研究

目的分析大肠腺瘤及腺瘤癌变组织中丝氨酸蛋白酶抑制剂Maspin（mammaryserine protease inhibitor）的表达。为临床诊断、治疗及预后判断提供新的理论依据。方法检测42例散发性大肠腺瘤伴上皮不同程度异型增生、50例大肠腺瘤癌变和40例大肠黏膜患者中Maspin和P53的免疫组化表达情况。结果大肠腺瘤癌变组患者Maspin和P53表达与大肠腺瘤组及对照组比较,差异均有统计学意义。且两者在大肠腺瘤癌变过程中呈负相关关系。结论 Maspin蛋白的丢失在大肠腺瘤癌变过程中起了一定的作用,可以作为提示大肠腺瘤预后的指标之一。