芪莲舒痞颗粒对慢性萎缩性胃炎癌前病变大鼠血管生成因子、VEGF的影响

目的:探讨芪莲舒痞颗粒(QLSP)治疗慢性萎缩性胃炎癌前病变的机制。方法:采用甲基硝基亚硝基胍(MNNG)、雷尼替丁加饥饱失常的方法,造成大鼠CAG癌前病变气虚血瘀证病结合的模型。给药后观察各组大鼠胃粘膜血管生成因子(VEGF)的变化。结果:胃粘膜癌前病变存在血管生成因子表达,而且与正常组有明显差异(P<0.05)。QLSP组能明显抑制血管生成因子VEGF的表达和分泌,并且与对照组有明显差异(P<0.05)。结论:芪莲舒痞颗粒能明显抑制血管生成因子的表达,此研究对本病的治疗提供了新的研究思路。

芪丹通脉片含药血清促血管生成的实验研究

目的:探讨芪丹通脉片含药血清对体内外血管生成的促进作用。方法:采用鸡胚绒毛尿囊膜模型(CAM),观测芪丹通脉片含药血清对CAM新生的促进作用;采用流式细胞术检测芪丹通脉片含药血清对内皮细胞周期的影响;采用免疫组织化学染色法检测内皮细胞VEGF的表达。结果:芪丹通脉片能够明显促进CAM血管新生,但弱于bFGF组;芪丹通脉片促进内皮细胞生长,增加细胞周期中S期细胞的数。芪丹通脉片能够上调VEGF的表达。结论:芪丹通脉片具有促进血管生成作用,其机制与促血管内皮细胞增殖以及上调VEGF的表达有关。

莪黄汤保留灌肠联合化疗对结、直肠癌组织VEGF表达的影响

目的:观察自拟中药方莪黄汤保留灌肠联合XELOX方案化疗对结、直肠癌组织血管生成因子(VEGF)表达的影响。方法:将治疗前30例患者作为对照组,行纤维结肠镜活检并保存肿瘤组织标本;然后随机分为2组各15例,均采用XELOX方案化疗,中药保留灌肠联合化疗组配合使用莪黄汤保留灌肠治疗。治疗后所有患者再次行肿瘤组织活检,并观察肿瘤组织中VEGF的表达情况。结果:化疗组、中药保留灌肠联合化疗组与对照组比较,肿瘤组织中VEGF的表达有一定下调;中药保留灌肠联合化疗组与化疗组比较,肿瘤组织中VEGF的表达稍有下调,但不明显。中药保留灌肠联合化疗可明显改善患者里急后重、腹痛等不适。结论:莪黄汤保留灌肠联合化疗能一定程度下调结、直肠癌组织中VEGF的表达。

TRAP阳性细胞及HIF-1α、VEGF、FGF-2表达在老年股骨头坏死修复反应中的分布及其意义

目的探讨股骨头坏死的修复反应机制。方法检测51例老年患者(≥60岁)人工关节置换术后股骨头标本的TRAP阳性细胞及缺氧诱导因子-1α(HIF-1α)、血管生成因子(VEGF)、纤维生成因子-2(FGF-2)表达的分布。结果耐酒石酸盐酸性磷酸酶(TRAP)阳性细胞主要存在于全部股骨头坏死修复区的过渡带,并随着放射学分期的进展,沿着修复区的过渡带向中心分布。HIF-1α表达在靠近坏死区的纤维坏死带和过渡带的内皮细胞;VEGF表达在修复区的水肿带;FGF-2则表达在整个修复区的血管壁和骨髓细胞。结论在晚期股骨头坏死的坏死区无HIF-1α、VEGF、FGF-2的表达,而参与修复区的血管生成反应;TRAP阳性细胞则出现在骨塌陷后的新生骨周围,并沿着新生血管向中心分布。

Glycer-AGEs-RAGE signaling enhances the angiogenic potential of hepatocellular carcinoma by upregulating VEGF expression

AIM:To investigate the effect of glyceraldehyde-derived advanced glycation end-products(Glycer-AGEs) on hepatocellular carcinoma(HCC)cells.METHODS:Two HCC cell lines(Hep3B and HepG2 cells)and human umbilical vein endothelial cells(HUVEC)were used.Cell viability was determined using the WST-8 assay.Western blotting,enzyme linked immunosorbent assay,and real-time reverse transcriptionpolymerase chain reactions were used to detect protein and mRNA.Angiogenesis was evaluated by assessing the proliferation,migration,and tube formation of HUVEC.RESULTS:The receptor for AGEs(RAGE)protein was detected in Hep3B and HepG2 cells.HepG2 cells werenot affected by the addition of Glycer-AGEs.GlycerAGEs markedly increased vascular endothelial growth factor(VEGF)mRNA and protein expression,which is one of the most potent angiogenic factors.Compared with the control unglycated bovine serum albumin(BSA) treatment,VEGF mRNA expression levels induced by the Glycer-AGEs treatment were 1.00±0.10 vs 1.92 ±0.09(P<0.01).Similarly,protein expression levels induced by the Glycer-AGEs treatment were 1.63±0.04 ng/mL vs 2.28±0.17 ng/mL for the 24 h treatment and 3.36±0.10 ng/mL vs 4.79±0.31 ng/mL for the 48 h treatment,respectively(P<0.01).Furthermore,compared with the effect of the control unglycated BSA-treated conditioned medium,the Glycer-AGEstreated conditioned medium significantly increased the proliferation,migration,and tube formation of HUVEC,with values of 122.4%±9.0%vs 144.5%±11.3%for cell viability,4.29±1.53 vs 6.78±1.84 for migration indices,and 71.0±7.5 vs 112.4±8.0 for the number of branching points,respectively(P<0.01).CONCLUSION:These results suggest that Glycer-AGEs-RAGE signaling enhances the angiogenic potential of HCC cells by upregulating VEGF expression.

垂体肿瘤转化基因和血管内皮细胞因子在子宫内膜异位症中的表达及意义

目的:检测PTTG及VEGF在子宫内膜异位症中异位内膜、在位内膜及对照组正常内膜的表达,并探讨其相关性。方法:选取52例子宫内膜异位症患者的异位内膜、44例在位内膜,27例正常子宫内膜组织为对照组。用逆转录聚合酶链式反应(RT-PCR)及免疫组化(SP)方法测PTTG、VEGF在三组中的表达情况。结果:PTTG mRNA在子宫内膜异位症中异位内膜组表达高于在位内膜组,在位内膜组表达高于正常子宫内膜组织(P<0.01,P<0.01)。PTTG蛋白表达在异位内膜组、在位内膜组、正常内膜组的阳性率分别为:90%、79%、22%,异位内膜组和在位内膜组表达均高于正常子宫内膜组织(P<0.01,P<0.01)。VEGF蛋白表达在异位内膜组、在位内膜组、正常内膜组的阳性率分别为:90%、84%、59%,异位内膜组和在位内膜组表达高于正常子宫内膜组织(P<0.01,P<0.01)。等级相关分析PTTG表达与VEGF表达呈正相关关系。结论:子宫内膜异位症中异位内膜组、在位内膜组均有PTTG mRNA及PTTG蛋白表达;且异位内膜组表达均显著高于在位内膜组及正常组;异位内膜组和在位内膜组中VEGF表达高于正常子宫内膜组织;PTTG高度表达可上调VEGF高表达,PTTG与VEGF呈正相关表达,提示子宫内膜活性增强、侵袭力增高,可促进血管形成。

(-)-Epigallocatechin-3-gallate inhibits growth of gastric cancer by reducing VEGF production and angiogenesis

AIM： To investigate the effect of （-）-epigallocatechin-3-gallate （EGCG） on growth of gastric cancer and its possible mechanism. METHODS： Heterotopic tumors were induced by subcutaneously injection of SGC-7901 cells in nude mice. Tumor growth was measured by calipers in two dimensions. Tumor angiogenesis was determined with tumor microvessel density （MVD） by immunohistology. Vascular endothelial growth factor （VEGF） protein level and activation of signal transducer and activator of transcription 3 （Star3） were examined by Western blotting. VEGF mRNA expression was determined by RT-PCR and VEGF release in tumor culture medium by ELISA. VEGF-induced cell proliferation was studied by MTT assay, cell migration by gelatin modified Boyden chamber （Transwell） and in vitro angiogenesis by endothelial tube formation in Matrigel. RESULTS： Intraperitoneal injection of EGCG inhibited the growth of gastric cancer by 60.4%. MVD in tumor tissues treated with EGCG was markedly reduced. EGCG treatment reduced VEGF protein level in vitro and in vivo. Secretion and mRNA expression of VEGF in tumor cells were also suppressed by EGCG in a dose-dependent manner. This inhibitory effect was associated with reduced activation of Star3, but EGCG treatment did not change the total Star3 expression. EGCG also inhibited VEGF-induced endothelial cell proliferation, migration and tube formation. CONCLUSION： EGCG inhibits the growth of gastric cancer by reducing VEGF production and angiogenesis, and is a promising candidate for anti-angiogenic treatment of gastric cancer.

Angiogenesis effects of adenovirus-mediated gene transfer of VEGF-B on chronic ischemic myocardium

Objective: To study the angiogenesis effects of adenovirus-mediated gene transfer of VEGF-B on chronic ischemic myocardium. Methods: Domestic pigs underwent thoracotomy and placement of an ameroid constrictor on the circumflex coronary artery. Four weeks later, Ad. VEGF-B, Ad. LacZ or PBS were administrated directly into the myocardium at 10 sites in the circumflex distribution (109 PFU or 100 μl) according to groups. Echocardiography and ex vivo coronary angiography were performed. The injection sites around myocardium were harvested and subjected to histological analysis and immunochemical staining. Results: E-chocardiography assessment 4 weeks after vector administration demonstrated significant improvement of regional wall systolic function. Collateral vessel development assessed by angiography was also significantly greater in Ad. VEGF-B animals than that in control animals. Vascular density analysis revealed a mean of 43±5 neovessels per high-power field in Ad. VEGF-B group versus 19±4 and 17±6 in Ad. LacZ and PBS group. Conclusion: Direct intramyocardial administration of Ad. VEGF-B can induce focal angiogenesis and result in improvement in regional myocardial function, which may be useful in patients with ischemic heart disease who are not eligible for conventional therapies.

Correlation of VEGF expression,angiogenesis and carcinomatous change in breast tumors

Objective: The aim of the study was to detect the expression of vascular endothelial growth factor (VEGF) and microvessel density (MVD) in breast benign tissues and malignant tumors to clarify the relationship between VEGF expression, angiogenesis and breast carcinoma occurrence. Methods: The expression of VEGF and MVD in 79 cases of invasive ductal breast carcinoma, 79 corresponding para-cancer normal tissues from primary invasive breast carcinomas, 35 breast carcinoma in situ, 23 breast atypical hyperplasia and 56 breast fibroid tumor were examined by immunohistochemistry staining (SP-method). Results: The positive rate of VEGF and MVD value increased significantly with the increase of the malignant degree of breast tissues (P = 0.000). In breast carcinoma group, the positive rate of VEGF and MVD value with lymph node metastasis were higher than those without lymph node metastasis (P = 0.011 and P = 0.023). A significant higher expression of VEGF and MVD value were observed as the clinical stage increased (P = 0.035 and P = 0.012). The MVD value was higher in VEGF positive group than negative group (P = 0.000). Conclusion: The combining detection of VEGF expression and MVD is helpful for evaluating malignant degree of breast carcinoma. Angiogenesis in breast tumors and occurrence of breast carcinoma might be correlated with the expression of VEGF.

Indomethacin suppresses growth of colon cancer via inhibition of angiogenesis in vivo

AIM: It has been reported that regular consumption of nonsteroidal anti-inflammatory drugs like indomethacin decreases the incidence and mortality rate of a number of gastrointestinal cancers. We aimed to explore the efficacy and possible mechanisms of indomethacin on tumor growth and tumor angiogenesis of human colon cancer xenografts in nude mice. METHODS: MTT (thiazolyl blue) assay was used to assess the effect of indomethacin on cultured human colorectal cancer cell line HCT116. HCT116 cells were inoculated subcutaneously into BALB/c-nu/nu mice. After oral administration of indomethacin, 3 mg/kg·d for 4 wk, animals were sacrificed by cervical dislocation. Immunohistochemical staining was employed to determine the microvessel density (MVD) and vascular endothelial growth factor (VEGF) expression in tumor tissues. RESULTS: Indomethacin, a non-selective COX inhibitor, significantly decreased the viability of HCT116 cells in a dose-dependent manner (P<0.05) with 50% inhibition at approximately 318.2±12.7 μmol/L Growth of HCT116 cell tumor was significantly suppressed by indomethacin. The tumor volume was significantly decreased in the treated group (458.89±32.07 mm3) compared to the control group (828.21±31.59 mm3) (P<0.05). The MVD of the treated group (19.50±5.32) was markedly decreased compared to the control group (37.40±4.93) (P<0.001). The VEGF expression of the treated group (1.19±0.17) was obviously reduced as compared to the control group (1.90±0.48) (P<0.01). The decrease in MVD was positively correlated with the decrease of VEGF expression (rs = 0.714, P<0.05). We did not see gastrointestinal complications in the treated group and no differences were noted in the body weight of the mice between the two groups throughout the study CONCLUSION: Indomethacin can significantly decrease the viability of cultured HCT116 cells and retard human colorectal HCT116 cell tumor growth via inhibiting tumor angiogenesis, which might be through reduction of VEGF expression.

Inhibitory activity of gold and silica nanospheres to vascular endothelial growth factor （VEGF）-mediated angiogenesis is determined by their sizes

Nanoparticles can be involved in biological activities such as apoptosis, angiogenesis, and oxidative stress by themselves. In particular, inorganic nanoparticles such as gold and silica nanoparticles are known to inhibit vascular endothelial growth factor （VEGF）-mediated pathological angiogenesis. In this study, we show that anti-angiogenic effect of inorganic nanospheres is determined by their sizes. We demonstrate that 20 nm size gold and silica nanospheres suppress VEGF-induced activation of VEGF receptor-2, in vitro angiogenesis, and in vivo pathological angiogenesis more efficiently than their 100 nm size counterparts. Our results suggest that modulation of the size of gold and silica nanospheres determines their inhibitory activity to VEGF-mediated angiogenesis.