Expression and correlation of CD44v6, vascular endothelial growth factor, matrix metalloproteinase-2, and matrix metalloproteinase-9 in Krukenberg tumor

AIM: To explore the expression and correlation of CD44v6, vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-2 and matrix metalloproteinase (MMP)-9 in Krukenberg and primary epithelial ovarian carcinoma. METHODS: The expressions of CD44v6, VEGF, MMP-2 and MMP-9 were detected by immunohistochemical method in 20 cases of normal ovarian tissues, 38 cases of Krukenberg tumor and 45 cases of primary epithelial ovarian carcinoma. RESULTS: The expression of CD44v6 (primary epithelial ovarian carcinoma tissue vs normal ovarian tissue: x2 = 4.516, P= 0.034; Krukenberg tumor tissue vs normal ovarian tissue: x2 = 19.537, P= 0.001) and VEGF (primary epithelial ovarian carcinoma tissue vs normal ovarian tissue: P = 0.026; Krukenberg tumor tissue vs normal ovarian tissue: x2 = 22.895, P= 0.001) was significantly higher in primary epithelial ovarian carcinoma tissue and Krukenberg tumor tissue than in normal ovarian tissue. The positive expression rate of MMP-2 and MMP-9 was 0% in the normal ovarian tissue. The positive expression rate of CD44v6 (x2 = 10.398, P= 0.001), VEGF (x2 = 13.149, P= 0.001), MMP-2 (x2= 33.668, P= 0.001) and MMP-9 (x2 = 38.839, P = 0.001) was remarkably higher in Krukenberg tumor than in primary epithelial ovarian carcinoma. The correlation of CD44v6, VEGF, MMP-2, and MMP-9 was observed in primary epithelial ovarian carcinoma and Krukenberg tumor. CONCLUSION: CD44v6, VEGF, MMP-2, and MMP-9 are involved in ovarian carcinoma, gastric cancer and Krukenberg tumor. Detection of CD44v6, VEGF, MMP-2 and MMP-9 may contribute to the diagnosis of ovarian carcinoma, gastric cancer, and Krukenberg tumor.     

血管内皮细胞生长因子在急性肺损伤大鼠中的表达及意义

目的探讨血管内皮细胞生长因子(VEGF)在脂多糖所致急性肺损伤大鼠中的表达及意义,为临床防治急性肺损伤提供参考依据。方法将40只SD大鼠随机分为LPS(脂多糖)组和NS(生理盐水)组,麻醉后气管插管,LPS组吸入LPS(3 mg/kg),NS组吸入等量NS。0h、2h、4h、6h时每组分别处死5只大鼠,抽血行血气分析,同时进行血浆VEGF水平、肺泡灌洗液(BALF)蛋白定量和VEGF水平、肺组织病理学、免疫组化以及VEGF mRNA表达水平检测。结果 LPS组2h、4h、6h时间点p H和Pa O2均明显低于NS组相应时间点,Pa CO2和肺损伤评分均明显高于NS组相应时间点(P0.05)。LPS组2h、4h、6h时间点BALF蛋白定量均明显高于NS组相应时间点(P0.05),LPS组2h、4h、6h时间点BALF和血浆VEGF定量均明显高于NS组相应时间点(P0.05)。LPS组BALF和血浆中VEGF水平与肺损伤评分均呈正相关(r=0.682和r=0.613,P0.001),BALF中VEGF水平与蛋白定量呈正相关(r=0.715,P0.001)。LPS组2h、4h、6h时间点肺组织中VEGF mRNA的表达均明显高于NS组相应时间点表达(P0.05)。结论 ALI大鼠血浆、BALF和肺组织中VEGF水平明显升高,血浆和BALF中VEGF水平与肺损伤程度呈正相关,BALF中VEGF水平与蛋白定量呈正相关,提示VEGF可能通过增加呼吸膜的通透性参与急性肺损伤发生过程。     

血管内皮细胞生长因子在糖尿病大鼠局灶性脑缺血再灌注模型中的表达

糖尿病大鼠局灶性脑缺血再灌注后各时间点血管内皮细胞生长因子在缺血中心区、半暗带区神经元和微血管的表达均明显低于非糖尿病大鼠。     

胃癌组织MMP-10和VEGF表达与血管生成的关系

目的:研究胃癌组织中基质金属蛋白酶- 10(MMP-10)、血管内皮生长因子(VEGF)和微血管密度(MVD)表达变化及其与肿瘤临床病理特征之间的关系.方法:以CD31作为MVD指标,应用免疫组化法检测60例胃癌组织和60例距病灶5 cm以上的正常组织中的MMP-10、VEGF和CD31的表达并对结果进行分析.结果:60例胃癌组织中的MMP-10、VEGF的表达阳性率分别为81.7%、76.7%,明显高于正常组织的表达阳性率11.7%、8.3%,两者差异有统计学意义(P<0.05).MMP-10、VEGF的表达与MVD、与肿瘤的分化程度、TNM分型、淋巴结的转移、浸润程度有关.结论:MMP-10、VEGF胃癌组织中高表达与胃癌侵袭转移、血管生成密切相关,可作为判断胃癌侵袭转移及预后的重要指标.     

Vascular endothelial growth factor modulates matrix metalloproteinase-9 expression in asthma

RATIONALE: Vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) are mediators of airway inflammation and remodeling in asthma. OBJECTIVES: This study investigates a potential relationship between VEGF and MMP-9, and the mechanisms by which VEGF signaling regulates MMP-9 expression in asthma. METHODS: We evaluated whether levels of VEGF correlated with levels of MMP-9 in the sputum of asthma patients, and the effect of VEGF receptor inhibitors on MMP-9 expression in murine model of asthma. Measurements and MAIN RESULTS: We have found that levels of VEGF and MMP-9 are significantly higher in the sputum of patients with asthma than in healthy control subjects, and a significant correlation is found between the levels of VEGF and MMP-9. This study with the ovalbumin-induced model of asthma revealed the following typical pathophysiologic features of asthma in the lungs: increased numbers of inflammatory cells of the airways, airway hyperresponsiveness, increased vascular permeability, and increased levels of MMP-9 and VEGF. Administration of VEGF receptor inhibitors reduced the pathophysiologic signs of asthma and decreased the increased expression of MMP-9 after ovalbumin inhalation. CONCLUSIONS: These results indicate that there is a close relationship between VEGF and MMP-9 expression and that inhibition of VEGF receptor down-regulates the expression of MMP-9. These findings suggest that VEGF signaling regulates MMP-9 expression and plays a critical role in initiation and maintenance of asthma.     

非小细胞肺癌组织MMP9、EGFR的表达及意义

目的检测非小细胞肺癌(NSCLC)组织中基质金属蛋白酶(MMP-9)和表皮生长因子受体(EGFR)的表达对NSCLC发生、发展的影响。方法分析其表达与肺癌发生、发展的相关性;结果 NSCLC组织中MMP-9、EGFR的表达均高于正常组织,其比较差异有显著性(P<0.05)。结论检测NSCLC的MMP-9、EGFR的表达对判断肿瘤的恶性程度和预后评估有一定的意义。     

Vascular endothelial growth factor correlates with matrix metalloproteinase-9 in the pleural effusion

Vascular endothelial growth factor (VEGF) is a potent, multifunctional cytokine that contributes to angiogenesis and inflammation. Matrix metalloproteinase-9 (MMP-9) is one of the major proteolytic enzymes that degrade various components of the extracellular matrix. Few data are available on the potential relationship between VEGF and MMP-9 in the accumulation of pleural effusion. We examined levels of VEGF and MMP-9 by means of enzyme immunoassay, zymographic analysis, and Western blot analysis in the patients with liver cirrhosis, tuberculosis, or lung cancer. The levels of VEGF and MMP-9 were significantly increased in the pleural fluids and sera of patients with tuberculosis and were even higher in patients with lung cancer compared with the patients with liver cirrhosis. A significant correlation was established between the level of VEGF and the level of MMP-9 in the pleural effusion. These results suggest that overproduction of VEGF and MMP-9 is associated with accumulation of the pleural effusion in tuberculosis and lung cancer. The relationship between VEGF and MMP-9 in the pleural effusion may have a role in the pathogenesis of pleural fluid formation.     

人脑胶质瘤中血管内皮细胞生长因子表达及其与细胞增殖的关系

为探讨人脑胶质瘤组织中血管内皮细胞生长因子 (VEGF)表达及其与细胞增殖的关系 ,应用链霉菌抗生物素蛋白 -过氧化物酶连接法 (SABC)免疫组织化学技术检测了 6 7例人脑胶质瘤、8例正常脑组织中 VEGF表达及增殖细胞核抗原 (PCNA)标记指数 (PCNA L I)。结果 VEGF在人脑胶质瘤组织中的阳性表达率为 83.6 %,正常脑组织中无表达 (P<0 .0 0 5 ) ;肿瘤组织中 VEGF表达与 PCNA L I呈显著正相关 (P<0 .0 0 5 )。认为胶质瘤细胞能分泌 VEGF,VEGF表达在肿瘤细胞增殖中起重要作用。     

Histologic features of venous invasion, expression of vascular endothelial growth factor and matrix metalloproteinase-2 and matrix metalloproteinase-9, and the relation with liver metastasis in pancreatic cancer

INTRODUCTION: Pancreatic cancer frequently is associated with venous invasion and hematogenous metastasis. AIMS: To determine morphologic features of invaded veins, intratumoral vascular composition, the correlation with liver metastasis, and expression of vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-2 and MMP-9, and the mechanism of development of hematogenous metastasis. METHODOLOGY: We examined 32 patients with resected pancreatic cancer: 18 had postoperative liver metastasis, and 14 had no liver metastasis. Specimens were examined to determine the composition of veins and microvessels by staining of victoria-blue and CD34. We also investigated expression of VEGF, MMP-2, and MMP-9 by immunohistochemical staining. RESULTS: Venous invasion was detected in 31 of 32 patients. Invaded venous densities of middle- and large-sized veins were significantly higher in patients with liver metastasis than in those with nonliver metastasis, and they were related to MMP-2 and MMP-9 overexpression. Invaded veins with fragmentation of the lumen through cancer cells were considered to be an intravasation of cancer (destroyed type vein), and their numbers were significantly related to liver metastasis, and MMP-2 and MMP-9 overexpression. CONCLUSION: In conclusion, almost all the patients with pancreatic cancer showed venous invasion, indicating that invasion into large veins and destroyed type veins could be a risk factor for liver metastasis and that increased expression MMP-2 and MMP-9 were related to such invasion.     

糖尿病大鼠缺血再灌注脑组织胰岛素受体表达与血管内皮生长因子的相关性

采用免疫组织化学技术检测糖尿病大鼠缺血脑组织胰岛素受体和血管内皮生长因子(VEGF)的表达特点.与单纯脑缺血组相比,糖尿病脑缺血组胰岛素受体和VEGF表达均明显降低(P＜0.05或P＜0.01);各组胰岛素受体与VEGF表达呈显著正相关(P＜0.05或P＜0.01).     

Thrombospondin-1 suppresses spontaneous tumor growth and inhibits activation of matrix metalloproteinase-9 and mobilization of vascular endothelial growth factor

Growth of tumors and metastasis are processes known to require neovascularization. To ascertain the participation of the endogenous angiogenic inhibitor thrombospondin-1 (TSP1) in tumor progression, we generated mammary tumor-prone mice that either lack, or specifically overexpress, TSP1 in the mammary gland. Tumor burden and vasculature were significantly increased in TSP1-deficient animals, and capillaries within the tumor appeared distended and sinusoidal. In contrast, TSP1 overexpressors showed delayed tumor growth or lacked frank tumor development (20% of animals); tumor capillaries showed reduced diameter and were less frequent. Interestingly, absence of TSP1 resulted in increased association of vascular endothelial growth factor (VEGF) with its receptor VEGFR2 and higher levels of active matrix metalloproteinase-9 (MMP9), a molecule previously shown to facilitate both angiogenesis and tumor invasion. In vitro, enzymatic activation of proMMP9 was suppressed by TSP1. Together these results argue for a protective role of endogenous inhibitors of angiogenesis in tumor growth and implicate TSP1 in the in vivo regulation of metalloproteinase-9 activation and VEGF signaling.     

基质金属蛋白酶在糖尿病患者动脉粥样硬化斑块中的表达

目的检测2型糖尿病患者动脉粥样硬化斑块内基质金属蛋白酶2(MMP2)和基质金属蛋白酶9(MMP9)的表达和分布,探讨MMP2和MMP9在糖尿病动脉粥样硬化斑块中表达的作用.方法从23例糖尿病足截肢和17例尸检下肢动脉标本中选取晚期动脉粥样硬化病变的组织126块,糖尿病组(74块),非糖尿病组(52块),从中随机选取各40块进行MMP2和MMP9抗原抗体的免疫组织化学染色,观察阳性物质在两组动脉粥样硬化斑块中的分布特点,利用计算机图像分析系统对染色程度作相对定量分析. 结果抗MMP2、抗MMP9免疫沉积物主要集中在斑块核心周围,特别是在斑块的肩部和纤维帽.糖尿病组动脉内膜抗MMP2免疫沉积物表达显著高于非糖尿病组[免疫沉淀物积分吸光度值(IA)69 014±14 459和57 004±16 171,阳性面积百分比(12.97±2.67)% 和(11.08±3.32)%,P<0.05];糖尿病组斑块内MMP9表达也显著高于非糖尿病组[IA 102 485±20 431和75 280±13 106,阳性面积百分比(18.35±3.59)%和(13.65±2.29)%,P<0.01]. 结论 MMP2和MMP9在糖尿病组动脉粥样硬化斑块中的表达显著高于非糖尿病组,MMP2和MMP9在糖尿病患者动脉中表达增强可以部分解释糖尿病患者易于发生动脉粥样硬化斑块破裂.     

血管内皮生长因子及其受体在肺气肿患者肺组织中的表达

目的探讨血管内皮生长因子(VEGF)及其受体2(VEGF受体2/KDR)在肺气肿患者肺组织中的表达及其与肺气肿的相关性。方法取35例行肺叶切除术患者[A组(吸烟伴肺气肿组)16例,B组(不吸烟肺功能正常组)14例,C组(吸烟但肺功能正常组)5例]的外周肺组织标本,ELISA法检测肺组织匀浆中VEGF的含量,免疫组化法检测KDR蛋白表达,RT PCR检测VEGF和KDRmRNA水平,TUNEL法检测肺泡隔细胞的凋亡。结果A组患者肺组织VEGF、KDR表达均低于B组(P<0.01),肺泡隔细胞凋亡率高于B组(P<0.01)。C组与B组相比,VEGF及KDR表达差异无统计学意义(P>0.05)。结论VEGF及KDR水平减少与肺泡隔细胞凋亡的增加可能与肺气肿的发生相关。     

Expression of tissue factor and vascular endothelial growth factor is associated with angiogenesis in colorectal cancer

We examined the expression of tissue factor (TF) and vascular endothelial growth factor (VEGF) and the microvessel density (MVD) in 100 patients with colorectal cancer, and we investigated the relationship of the expression of TF or VEGF with angiogenesis. TF antigen was positive in 57.0% of all specimens. Incidence of TF expression was 41.2%, 45.5%, 52.6%, 84.6%, and 81.3% in tumors from patients in clinical stages I, II, IIIA, IIIB, and IV, respectively. TF expression was correlated with the Dukes' classification (P = 0.01) and the clinical stage of colorectal cancer (P = 0.02). VEGF antigen was positive in 64.0% of all specimens. Incidence of VEGF expression was 41.2%, 57.6%, 73.7%, 84.6%, and 75.0% in tumors from patients in clinical stages I, II, IIIA, IIIB, and IV, respectively. VEGF expression was correlated with the Dukes' classification (P = 0.01) but showed a weak association with the clinical stage (P = 0.08). MVD was significantly associated with the depth of invasion (P = 0.01), lymph node metastasis (P = 0.001), and liver metastasis (P = 0.02). The mean values of MVD were 7.5 +/- 2.8, 10.1 +/- 5.7, 14.6 +/- 5.8, 13.5 +/- 3.9, and 15.9 +/- 4.2 in tumors from patients in clinical stages I, II, IIIA, IIIB, and IV, respectively. A close relationship between VEGF and MVD (P < 0.001) and a significant correlation between TF expression and MVD were observed (P = 0.02). TF-positive carcinomas presented high MVD and VEGF expression (P < 0.001) more frequently than did TF-negative tumors. These results suggest that involvement of TF in the process of metastasis and progression of colorectal cancer may depend on increased angiogenesis.     

基质金属蛋白酶-9和金属蛋白酶组织抑制物-1在IgA肾病肾组织中的表达

目的 探讨基质金属蛋白酶－9（MMP－9）／金属蛋白酶组织抑制物－1（TIMP－1）系统在IgA肾病肾组织中的表达及其对IgA肾病的进展的影响。方法 采用免疫组织化学和原位杂交技术,分别在蛋白质和基因水平检测38例IgA肾病患者肾组织中的MMP－9和TIMP－1的变化。结果 MMP－9在正常肾脏肾小球的脏层上皮细胞和内皮细胞有少量表达,在肾小管上皮细胞和间质血管壁也有少量表达;在IgA肾病中,MMP－9在系膜增殖性肾小球和间质血管壁的表达均明显增多（P＜0．001）,而在硬化肾小球内的表达则明显减少,肾小管细胞的MMP－9表达无明显变化。TIMP－1在正常肾组织中不能检出,在IgA肾病患者具有系膜增殖性病变的肾小球中有微量表达,在增殖在很重但尚未完全硬化的肾小球内表达增多,在肾小管间质表达最为明显（P＜0．001）,其主要见于肾小管细胞、间质细胞和血管内皮细胞。肾组织中的TIMP－1表达与血清肌酐水平呈显著相关（P＜0．05）,与肾小管间质的纤维化和炎细胞浸润程度亦明显相关（P值均＜0．01）。肾小球中的MMP－9表达与尿蛋白无明显相关性,但与血清肌酐水平呈显著负相关（P＜0．05）。结论 MMP－9和TIMP－1的异常表达可能是影响IgA肾病进展的因素之一。     

整合素β3与VEGFR-3在胃癌组织中的表达及意义

目的探讨整合素β3、血管内皮细胞生长因子受体-3（VEGFR-3）在胃癌发生、发展中的作用。方法用免疫组织化学SP法检测65份胃癌术后癌组织标本（观察组）中整合素β3、VEGFR-3表达[定量以淋巴管密度（LMVD）表示],并与20份距胃癌组织10 cm的正常胃黏膜组织标本（对照组）作对比。结果观察组整合素β3阳性表达率及LMVD均明显高于对照组（P均〈0.01）。观察组整合素β3阳性表达者LMVD明显高于阴性表达者（t=4.30,P〈0.01）,整合素β3阳性表达与LMVD呈正相关（r=0.473,P〈0.01）。结论整合素β3和VEGFR-3与胃癌的淋巴管形成及浸润转移密切相关,可作为胃癌预后综合性评估的有效指标。     

VEGF在类风湿关节炎滑液中的表达及上调MMP-2活性的研究

目的探讨血管内皮生长因子(VEGF)在类风湿关节炎(RA)患者关节滑液中的表达及其上调基质金属蛋白酶-2(MMP-2)活性在RA关节损伤机制中的意义。方法采用免疫印迹法、酶联免疫吸附试验、明胶酶谱电泳分析法及侵袭小室法,观察RA患者组及对照组关节滑液单个核细胞中VEGF及受体KDR的表达,单个核细胞上清液中VEGF的水平,VEGF与KDR阳性的单个核细胞体外共培养前后上清中MMP-2的活性及细胞侵袭力的变化。结果VEGF及KDR在滑液单个核细胞高表达；共培养后MMP-2的活性及细胞的侵袭力明显增强。结论VEGF与受体KDR结合促使RA滑液单个核细胞MMP-2活性上调及细胞侵袭力的增强,促进受损关节软骨及骨的降解破坏。     

血管内皮生长因子在胃癌中表达及其预后意义

目的研究血管内皮生长因子(VEGF)在胃癌组织中表达的临床意义.方法应用抗 VEGF 多克隆抗体的免疫组织化学方法,观察 VEGF 在胃癌组织中的表达,分析 VEGF 表达与不同监床病理因素及预后之间关系.结果 128例胃癌 VEGF 阳性表达率为64.1%;Ⅲ、Ⅳ期病人 VEGF 阳性表达率明显高于Ⅰ期患者(P<0.05);VEGF 阳性表达率与肿瘤的生长方式、浸润深度及淋巴线转移关系之间有显著统计学意义,肿瘤呈浸润型生长(71.8%)或浸及浆膜者(73.5%)明显大于膨胀型生长(52.0%)或无浆膜浸润者(53.3%)(P<0.025),淋巴结转移阳性肿瘤(75.0%)明显大于无淋巴结转移者(50.0%)(P<0.05);此外,在86例术后随访患者中,VEGF 阳性表达肿瘤患者的术后5年生存率明显低于 VEGF 阴性表达肿瘤患者(P<0.05).     

Expression of epidermal growth factor receptor, ErbB2 and matrix metalloproteinase-9 in hepatolithiasis and cholangiocarcinoma]

BACKGROUND/AIMS: Hepatolithiasis is a common disease in East Asia and presents as a histological feature of proliferative glands containing mucin. 5-10% of hepatolithiasis is known to be associated with cholangiocarcinoma. Recent studies reported that epidermal growth factor receptor (EGFR) could be activated through heparin binding- EGF cleavage by metalloproteinases. Matrix metalloproteinases (MMPs) which digest the extracellular matrix are required for cancer cell invasion and the expression of MMP-9 is known to be increased in cholangiocarcinoma. However, there has been few studies on the expressions and roles of EGFR and MMP in hepatolithiasis. This study was performed to clarify and compare the expressions of EGFR, erbB2 and MMP-9 in hepatolithiasis and cholangiocarcinoma. METHODS: Surgically resected liver tissues with hepatolithiasis (n = 14), cholangiocarcinoma (n = 20) and trauma (n = 2 as controls) were included. The expressions of EGFR, erbB2 and MMP-9 in tissue samples were examined by immunohistochemistry using respective monoclonal antibodies. RESULTS: In traumatic livers, the expressions of EGFR, erbB2 and MMP-9 were all negative. The expression of EGFR was increased in hepatolithiasis group (79%, 11/14) compared with cholangiocarcinoma group (25%, 5/20) (p < 0.05). The expression of erbB2 was detected only in cholangiocarcinoma (25%, 5/20). MMP-9 was increased in both hepatolithiasis (79%, 11/14) and cholangiocarcinoma (95%, 19/20) (p > 0.05). CONCLUSIONS: EGFR expression appears to be the dominant component in periductular hyperplasia of hepatolithiasis and MMP-9 is upregulated not only in cholangiocarcinoma but also in hepatolithiasis. This study suggests that EGFR and MMP-9 are associated with cholangiocarcinoma and hepatolithiasis.