EMMPRIN、HER-2蛋白表达与胃癌侵袭转移的关系

目的: 探讨细胞外基质金属蛋白酶诱导因子(EMMPRIN)、人表皮生长因子受体2(HER-2/neu)蛋白表达与人胃癌侵袭转移的关系, 以及2种蛋白表达之间的关系.方法: 应用量子点免疫荧光组织化学技术检测人胃癌组织芯片150芯(包括70例胃癌组织和5例正常胃黏膜组织)中EMMPRIN和HER2的蛋白表达, 并分析他们与临床病理特征的相关性.结果: 胃癌和正常胃黏膜组织中的EMMPRIN阳性表达率分别为72.86%和20.00%, 差异有显著性( P = 0.029). 在胃癌组织中HER-2蛋白的阳性率为47.14%(33/70), 高于正常胃黏膜组织, 但差异无显著性( P = 0.063).EMMPRIN、HER-2蛋白表达与胃癌患者年龄、性别、分化程度、肿瘤的浸润深度以及临床TNM分期之间差异均无显著性( P>0.05),仅与淋巴结转移显著相关( P<0.05). 在70例胃癌组织中EMMPRIN与HER-2蛋白表达之间呈显著正相关( r = 0.383, P = 0.001).结论: EMMPRIN与HER-2/neu可能协同促进了胃癌的淋巴结转移.     

EMMPRIN和MT1-MMP在肝细胞肝癌中的表达及临床意义

目的 研究基质金属蛋白酶诱导因子(EMMPRIN)和模型金属蛋白酶1(MT1-MMP)在肝细胞肝癌中的表达及其与肝癌临床病理生物学行为之间的关系.方法 采用免疫组化方法检测40例肝癌手术切除标本的EMMPRIN及MT1-MMP的表达情况.结果 ①MT1-MMP和EMMPRIN在肝癌组织中阳性表达率分别为62.5%和52.5%,明显高于在正常肝组织中的阳性表达率(P均<0.01);②EMMPRIN与肿瘤的转移、肝癌组织分化程度、肿瘤的大小有关;③MT1-MMP与肿瘤的转移、肿瘤的大小有关,与分化程度无关;④MT1-MMP蛋白与EMMPRIN蛋白在肝癌中的表达呈正相关(r=0.608, P<0.05).结论 MT1-MMP和EMMPRIN的表达均与肝癌的浸润转移有关,MT1-MMP和EMMPRIN的检测对于评估肝癌的预后有一定意义.     

TIMP-2、MMP-2和MT1-MMP在活化肝星状细胞中的表达及对细胞外基质合成分泌的影响

目的 研究金属蛋白酶组织抑制剂-2(TIMP-2)、基质金属蛋白酶-2(MMP-2)和膜型基质金属蛋白酶-1(MT1-MMP)在活化肝星状细胞(HSCs)中的表达,观察其对细胞外基质(ECM)合成分泌的影响.方法 原代分离培养大鼠HSCs活化后,分别给予40～160 pmol化学合成经修饰抗TIMP-2 siRNA进行干预,检测培养细胞上清液透明质酸(HA)、Ⅲ型前胶原(PCⅢ)和羟脯氨酸(Hyp)的含量,采用荧光实时定量PCR法检测TIMP-2、MMP-2、MT1-MMP、MMP-13、COL Ⅰ和COL Ⅲ mRNA的表达,western印迹检测TIMP-2、MT1-MMP和MMP-13蛋白表达及明胶酶谱法检测MMP-2蛋白表达.结果 应用化学合成经修饰抗TIMP-2 siRNA后,TIMP-2、MMP-2、MT1-MMP、COL Ⅰ和COL Ⅲ的表达明显降低,而MMP-13的表达则明显增加,培养细胞上清液中HA、PCⅢ和Hyp的含量也明显减少.结论 TIMP-2通过MT1-MMP介导MMP-2的活化,抑制TIMP-2的表达,MT1-MMP和MMP-2的表达随之降低,而HSCs合成分泌ECM也相应减少.     

EMMPRIN及MMP-7在膀胱移行细胞癌中的表达及意义

应用免疫组织化学技术检测60例膀胱移行细胞癌患者癌组织（TCC组）和8例正常膀胱组织（对照组）中细胞外基质金属蛋白酶诱导因子（EMMPRIN）和基质金属蛋白酶-7（MMP-7）表达情况,分析其表达与TCC分级、分期的关系。结果对照组EMMPRIN和MMP-7无表达,而TCC组表达较强,其中EMMPRIN阳性表达42例,MMP-7阳性表达40例。二者表达均与肿瘤的病理分级显著相关,而与肿瘤的临床分期无明显相关性。认为EMMPRIN和MMP-7的阳性表达与TCC的恶性程度有关,可作为判断TCC预后的指标。     

MT1-MMP对人肝癌细胞浸润能力的影响

目的 观察膜型基质金属蛋白酶-1(MT1-MMP)对人肝癌细胞株浸润能力的影响,并初步探讨其作用机制.方法 将稳定表达MT1-MMP基因转染至HepG2细胞中,应用Western印迹法检测MT1-MMP蛋白表达;明胶酶谱分析法检测MMP-2酶原活性;体外侵袭实验检测细胞株浸润能力.结果 重组质粒转染株MT1-MMP蛋白表达水平明显高于空质粒组和未转染组(P＜0.01).明胶酶谱分析实验发现,MT1-MMP组同时检测到72000酶原形式和64000活性形式的MMP-2,另两组只检测到72000酶原形式的MMP-2.体外侵袭实验结果显示,MT1-MMP组细胞穿过基质胶(Matrigel)的细胞数目明显多于其他两组(P＜0.01).结论 MT1-MMP能显著增强肝癌细胞株的浸润能力,其机制主要是通过激活MMP-2-酶原,降解肿瘤周围的基质成分实现的.     

膜型基质金属蛋白酶1在胃癌及癌周组织中的表达及临床意义

目的探讨膜型基质金属蛋白酶1(MT1-MMP)在胃癌及其周围组织中的表达和临床意义。方法收集胃癌病例110例,利用免疫组化染色、RT-PCR分析MT1-MMP在手术切除肿瘤组织及瘤旁组织中表达的差异,以及与患者临床特点及预后的关系。结果 110例肿瘤标本根据染色结果评定,高表达组(>4分)74例,低表达组(≤4分)36例,而瘤旁组织仅有5例呈低表达,其余均未见明显表达。RT-PCR显示Ⅰ、Ⅱ期胃癌与Ⅲ、Ⅳ期胃癌之间表达也具有统计学差异(P<0.05),不同组织类型的胃癌之间表达无明显差异。患者肿瘤早期转移、2年复发率及生存率与MT1-MMP表达具有一定的相关性。结论 MT1-MMP在胃癌组织中表达明显高于癌旁肿瘤组织,与胃癌的病理类型无关,而与胃癌的分期有关。MT1-MMP高表达的胃癌患者,其预后往往差于低表达患者。MT1-MMP有可能作为胃癌治疗的一个新的靶向基因位点。     

CD44v6、MT1-MMP和VEGF在肝细胞肝癌中的表达及意义

采用免疫组化法检测40例肝细胞肝癌(简称肝癌)及10例正常肝组织手术切除标本的血管内皮生长因子(VEGF)、黏附分子(CD44v6)和膜型金属蛋白酶-1(MT1-MMP)的表达情况.结果MT1-MMP、CD44v6和VEGF在肝癌组织中阳性表达明显高于正常肝组织(P均＜0.01);MT1-MMP和VEGF与肿瘤的转移、大小有关,与组织分化程度无关;CD44v6与肿瘤的转移、分化程度有关,与大小肿瘤无关;MT1-MMP与CD44v6、CD44v6与VEGF、MT1-MMP与VEGF在肝癌组织中的表达均呈明显正相关(r=0.506、0.701、0.566,P均＜0.01).提示MT1-MMP、CDd4v6、VEGF联合检测有助于肝癌的生物学行为判断和预后评估.     

胃癌组织中MMP-9mRNA、TIMP-1mRNA的表达变化及意义

目的观察基质金属蛋白酶（MMP）-9及其抑制剂（TIMP一1）在胃癌组织中的表达变化,并探讨两者在胃癌发生、发展中的作用。方法采用逆liT—PCR法检测43份胃癌组织、35份癌旁组织和8份胃溃疡组织中MMP-9和TIMP-1的mRNA表达,分析两指标表达的相关性及与胃癌临床病理特征的关系。结果胃癌组织中MMP一9mRNA、TIMP一1mRNA表达均显著高于癌旁组织和胃溃疡组织,尤以T。级、有淋巴结转移、Ⅲ期者为著（P均〈0．05）;MMP-9mRNA、TIMP一1mRNA表达均与胃癌患者性别、年龄、肿瘤大小及分化程度无关,与浸润深度、淋巴结转移及临床分期有关（P均〈0．05）。结论胃癌组织中MMP-9mRNA、TIMP一1mRNA的表达升高,且与肿瘤浸润、侵袭有关。     

胃癌组织中HIF-1α和MMP-9的表达及意义

采用免疫组化SP法检测120例胃癌组织中缺氧诱导因子(HIF)-1α和基质金属蛋白酶(NMP)-9的表达情况,分析二者与胃癌临床病理特征的关系.结果本组标本中HIF-1α和MMP-9阳性表达率未55.8%和35.8%,二者在胃癌组织中的阳性表达率与肿瘤分化程度、临床分期相关;HIF-1α阳性表达率与肿瘤直径相关,而:MMP-9的表达同淋巴结转移相关;HIF-1α,MMP-9蛋白在胃癌组织中的阳性表达率呈正相关(r=0.216,P<0.05).认为HIF-1α、MMP-9蛋白与胃癌的生长、侵袭、转移密切相关.     

MT1-MMP对人肝癌细胞株HepG2生物学行为的影响

目的 观察膜型基质金属蛋白酶-1(MT1-MMP)对人肝癌细胞株HepG2生物学行为的影响.方法 将稳定表达MT1-MMP基因转染至HepG2细胞中,应用RT-PCR、Ⅰ型胶原黏附和Matrigel侵袭小室实验,检测细胞MT1-MMP mRNA水平,体外黏附、侵袭和迁移能力的变化.结果 重组质粒转染株MT1-MMP mRNA表达水平明显高于空质粒组和对照组(P<0.01).MT1-MMP明显提高细胞Ⅰ型胶原黏附、迁移和Matrigel侵袭能力(P<0.01).结论 MT1-MMP过表达可促进HepG2细胞体外侵袭和转移,提示其可作为人肝癌抗侵袭治疗的分子靶点.     

Immunoexpression of cyclooxygenase-2 in primary gastric carcinomas and lymph node metastases

AIM: To evaluate immunoexpression of cyclooxygenase-2 (COX-2) in primary gastric carcinomas and respective lymph node metastases.METHODS: Immunohistochemistry to analyze COX-2 expression was performed on tissue microarray slices obtained from 36 specimens of gastrectomy and satellite lymph nodes from patients with gastric carcinoma.RESULTS: Immunostaining was seen in most cases, and COX-2 expression was higher in lymph node metastases than in corresponding primary gastric tumors of intestinal, diffuse and mixed carcinomas, with a statistically significant difference in the diffuse histotype (P = 0.0108).CONCLUSION: COX-2 immunoexpression occurs frequently in primary gastric carcinomas, but higher expression of this enzyme is observed in lymph node metastases of the diffuse histotype.     

Significance of Survivin and PTEN expression in full lymph node-examined gastric cancer

AIM:To study the relationship between Survivin andPTEN expression and lymph node metastasis,depth ofinvasion and prognosis of gastric cancer patients in Chi-na.METHODS:Specimens of gastric cancer tissue were col-lected from the Affiliated Hospital of Jianghan University.All the 140 patients had complete examination data.Alllymph nodes were found by the fat-clearing method.Theinterrupted serial 4-micron sections,routine hematoxylinand eosin staining and immunohistochemical methodswere used to detect the lymph node metastases.Gastriccancer tissue microarray was performed to test the ex-pression of Survivin and PTEN(17A)in gastric cancer byimmunohistochemical method.All data were processedusing x~2 test,Fisher's exact test,Kaplan-Meyer Log-rankmethod and Cox multivariate analysis(SPSS 12.0 soft-ware).RESULTS:One hundred and eighteen specimenswere used in our tissue microarray(utilization rate was82.4%).A total of 7580 lymph nodes were found.Metas-tases were found in 90 specimens and 1618 lymph nodeswere detected.The positive rate of Survivin and PTENexpression was 52.5%(62/118)and 76.2%(90/118),respectively.A highly positive correlation was found be-tween Survivin and PTEN expression(x~2=4.17,P=0.04).Survivin expression was positively correlated with UICCN stage(x~2=8.69,P=0.03)and histological classifica- tion(x~2=4.41,P=0.04)by x~2 tests.PTEN expression waspositively correlated with depth of invasion(P=0.02)andhistological classification(x~2=5.47,P=0.02).But Survivinand PTEN expressions were not related with prognosis ofgastric cancer patients.A significant correlation betweenlymph node metastasis and prognosis was demonstratedby Cox multivariate analysis(x~2=4.85,P=0.028).CONCLUSION:Survivin is positively correlated withPTEN expression in gastric cancer and is a molecularmarker of lymph node metastasis while PTEN expressionis a molecular marker of advanced gastric cancer.UICCN stage is the most important prognostic factor of gastriccancer in China.     

Levels of matrix metalloproteinase-1 and tissue inhibitors of metalloproteinase-1 in gastric cancer

AIM:To evaluate the levels of preoperative serum matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in gastric cancer.METHODS:One hundred gastric cancer patients who underwent gastrectomy were enrolled in this study.The serum concentrations of MMP-1 and TIMP-1 in these patients and in fifty healthy controls were determined using an enzyme-linked immunosorbent assay.RESULTS:Higher serum MMP-1 and TIMP-1 levels were observed in patients than in controls (P < 0.001).Serum M...     

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。     

Increased expression of matrix metalloproteinase-9 associated with gastric ulcer recurrence

AIM: To compare matrix metalloproteinase (MMP)-9 and tissue inhibitor of metalloproteinase (TIMP)-1 in gastric ulcer (GU) and chronic superficial gastritis (CSG). METHODS: This study enrolled 63 patients with GU and 25 patients with CSG. During upper gastroduodenal endoscopy, we took samples of gastric mucosa from the antrum and ulcer site from patients with GU, and samples of antral mucosa from patients with CSG. Mucosal biopsy tissues were cultured for 24 h, and the culture supernatant was measured for levels of MMP-9 and TIMP-1. After receiving eradication therapy for Helicobacter pylori (H. pylori ) and 8 wk proton-pump inhibitor therapy for GU, follow-up endoscopy examination was performed after 6 mo and whenever severe symptoms occurred. RESULTS: Levels of MMP-9 and TIMP-1 at the ulcer site or in the antrum were significantly higher in GU than CSG patients. MMP-9 levels at the ulcer site were significantly higher than in the antrum in GU patients, and had a significantly positive correlation with TIMP-1. MMP-9 levels were significantly higher in H. pylori -positive than H. pylori -negative GU and CSG patients. Levels of MMP-9 or TIMP-1 at the ulcer site were associated with the histological severity of activity and inflammation. About 57 GU patients were followed up, and seven had GU recurrence. H. pyloriinfection and MMP-9 levels were risk factors for the recurrence of GU adjusted for age and sex by multiple logistic regression analysis. CONCLUSION: MMP-9 may perform an important function in gastric ulcer formation and recurrence.     

COX-2基因表达与胃癌淋巴结转移的关系

目的 研究COX-2 mRNA及蛋白在胃癌组织中的表达,探讨COX-2与胃癌淋巴结转移的关系。方法 采用 RT-PCR方法检测30例新鲜胃癌标本及相匹配的癌旁正常组织COX-2 mRNA的表达;用免疫组化方法检测45例胃癌石蜡标本COX-2蛋白表达。结果 胃癌组织中存在COX-2 mRNA(73.3％)及蛋白(62.2％)表达。伴淋巴结转移者,COX-2 mRNA及蛋白表达高于无转移者,(P<0.05)。结论 COX-2基因在胃癌中表达增高,且与胃癌淋巴结转移明显相关。     

卵巢浆液性腺癌组织中MMP-2、MT1-MMP的表达变化及意义

目的观察卵巢浆液性腺癌中的基质金属蛋白酶-2（MMP-2）、膜型基质金属蛋白酶-1（MT1-MMP）的表达变化。方法采用免疫组化PV6000法检测50例卵巢浆液性腺癌、30例卵巢交界性浆液性腺瘤和30例卵巢良性浆液性腺瘤组织中的MMP-2、MT1-MMP。结果MMP-2和MT1-MMP在卵巢浆液性腺癌和交界性浆液性腺瘤中的表达阳性率高于良性浆液性腺瘤（P〈0．05）。卵巢良性浆液性腺瘤组织中的MMP-2、MT1-MMP与病理分级、淋巴结转移、临床分期和预后有关（P均〈0．0．5）。卵巢浆液性腺癌中MMP-2、MT1-MMP的表达呈正相关（L=0．61,P〈0．01）。结论卵巢浆液性腺癌中MMP-2、MT1-MMP表达上调。二者在卵巢浆液性腺癌的发生、浸润和转移中过程中协同发挥重要作用,可作为判断肿瘤恶性程度和预后的重要指标。     

AKT-p27Kip1-Cyclin E在胃癌组织中的表达及意义

目的:探讨AKT、p27Kip1与Cyclin E表达在胃癌发生发展中的意义.方法:收集2008-01/2010-01湘潭市第一人民医院和南华大学附属南华医院的活检标本和胃癌手术切除标本,包括正常胃黏膜组织14例（胃镜活检标本）、非典型增生胃组织10例（胃镜活检标本）、胃癌组织94例、癌旁组织49例,淋巴结转移胃癌组织...     

胰腺癌中细胞外基质金属蛋白酶诱导剂的表达及临床意义

目的 检测细胞外基质金属蛋白酶诱导剂（EMMPRIN）在胰腺癌中的表达及其与P糖蛋白（P-gp）、血管内皮生长因子（VEGF）的关系，以探讨胰腺癌细胞多药耐药和浸润转移是否有关联。方法 应用免疫组化SP法检测34例胰腺癌患者癌组织中EMMPRIN、P-gp和VEGF的表达，用卡方检验和相关分析了解其与临床病理参数的关系。结果 EMMPRIN、P-gp和VEGF在胰腺癌组织中阳性表达率分别为61．8％、55．9％和64．7%。EMMPRIN、P-gp、VEGF阳性表达与性别、年龄、肿瘤大小及病理分化程度无关（P〉0．05），但与淋巴结转移有关（P〈0．05）。EMMPRIN表达与P-gp、VEGF分别相关（r=0．398和r=0．432，P〈0．05）。结论 胰腺癌中EMMPRIN与P-gp、VEGF表达有关，提示肿瘤耐药、浸润和转移之间有一定相关性，EMMPRIN可能是其中的关键因子。     

Increased expression and cell surface localization of MT1-MMP plays a role in stimulation of MMP-2 activity by leptin in neonatal rat cardiac myofibroblasts

Myocardial matrix remodeling is a well-recognized disease modifier in the pathogenesis of heart failure, although the precise underlying molecular mechanisms remain to be elucidated. Here we investigated the effects of leptin, circulating levels of which are typically increased in obese individuals, on MMP and collagen expression and MMP activity in isolated cardiac myofibroblasts. Neonatal rat myofibroblasts were treated with 6 nM recombinant leptin and the collected supernatant analyzed for MMP-2 activity via gelatin zymography. MMP-2, MT1-MMP and procollagen-I and -III protein expression were determined by western blotting and MMP-2 and MT1-MMP mRNA expression were examined utilizing real-time PCR. Procollagen-I levels were analyzed by confocal microscopy and collagen synthesis was determined through [³H]-proline incorporation. Exposure of myofibroblasts to leptin (24 h) significantly increased MMP-2 activity, while mRNA and protein levels remained unchanged. Leptin also significantly enhanced mRNA and protein expression of MT1-MMP, a known activator of MMP-2. Biotinylation assays indicated increased cell surface expression of MT1-MMP in response to leptin and use of a MT1-MMP inhibitor attenuated the leptin-mediated elevation of MMP-2 activity. Total cellular collagen synthesis was unaffected by leptin treatment, however intracellular procollagen-I protein was significantly increased in treated cells. Furthermore, extracellular soluble procollagen-I was increased, while a decrease in soluble procollagen-III protein was observed in conditioned media. In summary, these findings in isolated cardiac myofibroblasts support the suggestion that leptin may directly influence myocardial matrix metabolism, and this may represent a mechanism contributing to cardiac fibrosis in obese patients with elevated plasma leptin levels.