Esophageal cancer is one of the common malignant tumors with high incidence and poor prognosis. Angiogenesis-related pathways play an important role in the occurrence and development of esophageal cancer. Vascular endothelial growth factor (VEGF) is the main mediator of angiogenesis. In addition to promoting angiogenesis and maintaining the survival of neovascularization, VEGF can also directly act on esophageal cancer cells and promote the occurrence and development of tumors. This article reviews the biology of VEGF and its effect on blood vessels, the expression of VEGF in esophageal cancer cells and its influencing factors, the role of VEGF in esophageal cancer cells, the immunomodulatory activity of VEGF and the clinical study of VEGF inhibitors. The purpose of this study is to provide a basis for more rational use of VEGF inhibitors in the treatment of esophageal cancer.
For research the relationship between the expression of vascular endothelial growth factor (VEGF) and the cell proliferation. The expression of VEGF was evaluated while the cell cycle of hepatoma cell line Hep G2, which was synchronized at G0 phase with serum deprivation, and reinitiated with TPA and blocked with antisense oligonucleotides of c-jun. Results: Hep G2 cell did not express VEGF at G0 phase. TPA could induce the expression of VEGF as well as initiation of cell cycle. The antisense oligonucleotides of c-jun could prohibit the expression of VEGF and arrest the cell cycle at G0 phase. Conclusion: The fact that the expression of VEGF accompanies the initiation of cell cycle suggests that they be regulated by the same singnal pathway, the expression of VEGF may be a marker indicating the proliferation of hepatoma cells.
Objective To evaluate the effect on microvessel density (MVD) and vascular endothelial growth factor (VEGF) expression of combining radiofrequency ablation (RFA) with arsenious acid (AA) locally treating liver VX2 tumor in rabbits. Methods Twenty-eight New Zealand White rabbits with implanted liver VX2 tumors were randomly divided into four groups, control group (n=7), AA group (n=7), RFA group (n=7) and combination (RFA+AA) group (n=7). All rabbits were killed 14 days after treatment. MVD and VEGF expression were examined by immunohistochemistry. Results The MVD degraded one by one in control group,AA group,RFA group and RAF+AA group, which were (38.50±0.44), (23.07±0.47), (18.65±0.39) and (11.36±0.36)/HP respectively, compared while each two groups, P＜0.05. The VEGF expression also degraded one by one, the ratio of positive cases were 7/7, 5/7, 4/7 and 2/7 respectively, compared while each two groups, P＜0.05. There was positive correlation between VEGF expression and MVD (Person conefficient of product-moment correlation r=0.47, P＜0.01). Conclusion Combining RAF with AA therapy can greatly decrease MVD and VEGF expression of tumor tissue.
Objective To observe the degradation of the polyactic glycolate acid (PLGA) microparticles with releasing-slowly vascular endothelial growth factor(VEGF) synthesized by the method of emulsification-diffusion. Methods The method of emulsification-diffusion is to incorporate VEGF into microparticles composed of biodegradable PLGA. The controlled release of microparticles are acquired. The content of the VEGF released slowly from PLGA microparticles in vitro was detected with ELISA at different time. Results We synthesized 100 releasing-slowly VEGF PLGA microparticles with the size of 0.20-0.33 μm by 5 times. The contents were 62±11 ng/L, 89±14 ng/L, and 127±19 ng/L in the 1st, the 2nd and the 3rd months after degradation, respectively. Conclusion The PLGAmicroparticles with releasing-slowly VEGF can be synthesized by the method of emulsification-diffusion.
Objective To investigate the expressions of monocyte chemoattractant protein-1 (MCP-1) and vascular endothelial growth factor (VEGF) in gastric cancer tissues and normal gastirc mucosa tissues and the situation of helicobacter pylori (HP) infection, and detect their relationships and clinicopathologic significances. Methods Expressions of MCP-1 and VEGF were detected by immunohistochemistry in gastric cancer tissues and normal gastric mucosa tissues (5-10 cm from the mass), and HP was detected in specimen from gastric antrum by Giemsa dyeing method. Results MCP-1 and VEGF expressions in gastric cancer tissues were significantly higher than those in normal gastric mucosa tissues (P＜0.05), but there was no difference in HP positive and negative tissues included the cancer and the normal tissues （P＞0.05）. The expressions of MCP-1 and VEGF in carcinoma with tumordiameter ＞5 cm, poorly differentiated， lymph node metastasis， distant metastasis and Ⅲ+Ⅳ stage of TNM were significantly higher than those with tumor diameter ≤5 cm, well and moderately differentiated， non-lymph node metastasis， non-distant metastasis and Ⅰ+Ⅱ stage of TNM (P＜0.05). Conclusion The high expressions of MCP-1 and VEGF in gastric cancer may relate to tumor angiogenesis and metastasis, but HP infection may be irrelevant.
The intervention therapy targeting vascular endothelial growth factor (VEGF) has become a specific and effective method for the treatment of diabetic retinopathy (DR). However, some patients did not respond or responded poorly to anti-VEGF therapy, and its effects of eliminating edema and improving vision appear to be unstable in the same patient. Hypoxia-inducible factor-1α (HIF-1α), an important upstream transcriptional regulator of VEGF, is an oxygen concentration-sensitive protein expressed in tissues under hypoxia. It can simultaneously target many downstream target genes except VEGF, such as placental growth factor and angiopoietin-like protein 4, to cause blood-retinal barrier damage and neovascularization, and thus participate in various pathological changes of DR to promote the occurrence and development of DR. Therefore, direct intervention of HIF-1α or targeting one or more downstream target genes regulated by HIF-1α to treat DR may have better efficacy. In the future, the development of effective and safe HIF inhibitors or anti-VEGF with HIF-1α other target gene inhibitors may have broader clinical application prospects.
Objective To observe the influence of rAAV-mediated antisense vascular endothelial growth factor (rAAV-aVEGF165) on the expression of retinal VEGF in diabetic rats. Methods 40 Sprague-Dawley rats induced diabetic rat model by intraperitoneal injection with streptozotocin (STZ). 32 rats were involved in study besides death and blood sugar recovery in experimental process, 16 spragud-Dawleg (SD) rats were received intravitreal injection with rAAV-aVEGF165 (1010 pfu) as experimental group, another group of Sprague-Dawleg (SD) rats were injected with phosphate buffered saline (PBS) as control group. One and five month after model establishment, the expression of retinal VEGF was evaluate by immunhistochemistry and Western blot; the retinal vasular was examined by transmission electron microscopy. Results On 1 month,the expression of retinal VEGF was lowest in each group. On 5 month, the expression of retinal VEGF was decreased in experimental group which compared to control, the difference are statistically significant （t=23.87,Plt;0.01）. The transmission electron microscopy results showed that retina has no obvious chages in experimental group, however,contral group showed fragmental thickening and splitting of basement membrane, swelling and deformation of endothelia cells,fingerlike prcess into the capillary cavity,and uneven distibution of heterochromatin in pericytes. Conclusion rAAV-aVEGF165 can reduce the expression of retinal VEGF thereby preventing occurrence and development of diabetic retinopathy. rAAV is an effective vectors of eye antisense gene. （Chin J Ocul Fundus Dis，2008，24：255-258）
ObjectiveTo explore the effect and mechanisms of bone marrow mesenchymal stem cells (BMSCs) on healing quality of acetic acid-induced gastric ulcer. MethodsForty-eight clean grade male Wistar rats were used to establish the model of gastric ulcer with acetic acid and were randomly divided into 3 groups after 3 days of modeling, 16 rats each group. After the abdominal cavity was open and stomach was pulled out, no treatment was given in group A, 150 μL phosphate buffered saline (PBS) and 150 μL BMSCs at passage 4+PBS (1×108 cells/100 μL) were injected into the gastric wall surrounding the ulcer at 5 different points in groups B and C respectively. After 10 days, the ulcer area was measured, the mucosal thickness and the number of dilated glands were tested in the regenerative mucosa by histological method. And the expression of vascular endothelial growth factor (VEGF) was detected at ulcerative margin by immunohistochemical method. ResultsThe ulcer area in group C was significantly smaller than that of groups A and B (P<0.01), but no significant difference was found between groups A and B (P>0.05). HE staining showed that group C had thicker regenerative gastric mucosa, less dilated glands, and more regular mucosal structure than groups A and B, showing significant differences in regenerative gastric mucosa thickness and dilated glands number (P<0.01), but no significant difference between groups A and B (P>0.05). Immunohistochemical staining showed that the positive expression of VEGF in the ulcer margin mucosa of group C was significantly higher than that of groups A and B. The integral absorbance (IA) value of VEGF expression in group C was significantly higher than that in groups A and B (P<0.01), but no significant difference between groups A and B (P>0.05). ConclusionBMSCs can accelerate ulcer healing by the secretion of VEGF, and improve the quality of ulcer healing.
bjective To investigate the correlation between expression of vascular endothelial growth factor(VEGF) of serum and tumor tissues and the clinical prognosis in patients with breast cancer. Methods The expressions of VEGF level of serum and tumor tissues in 44 patients with invasive duct breast cancer, 13 with benign breast diseases and 40 healthy controls. Serum VEGF level was measured by ELISA method. The protein expression of tissue VEGF, ER and C-erbB-2 were evaluated by immunohistochemistry LSAB method. Results Serum VEGF level and tissue VEGF expression in breast cancer were higher than those in benign breast diseases （P＜0.001）, and there was no significance in benign breast diseases and healthy controls （Pgt;0.05）. VEGF expression was correlated with lymph node metastasis (P＜0.01), ER and C-erbB-2 expression (P＜0.05, P＜0.01) and clinical stage （P＜0.01）. There were no statistical correlation between VEGF expression and age, tumor size (Pgt;0.05). Conclusion There is positively correlation between serum VEGF level and tissue VEGF expression, and between VEGF expression and clinic prognosis. Serum VEGF level may be one of important index of prognosis estimation in patients with breast cancer.
Objective To compare the transfection effects on soluble fms-like tyrosine kinase receptor-1 (sFlt-1) gene (2-4 transcellular region) mediated by carboxymethylated dextran coated nanoparticle and lipofectamineTM2000.Methods The plasmid pcDNA3.1-EGFP/sFlt-1(2-4) was constructed and assessed by enzyme cut, electrophoresis, and genetic sequencing. Three groups were divided: nanoparticle group, lipofectamine group, and non-transfected group. Twenty-four and 48 hours after the transfection, the distribution of cellular green fluorescence was oberved under the inverted phase contrast fluorescence microscope; the expression rate of green fluorescence was measured by flow cytometry; the expression of sFlt-1(2-4)mRNA and the protein was detected by reverse transcriptionpolymerase chain reaction (RT-PCR) and Western blot; the growth of the cells was observed by methyl thiazolyl tetrazolium (MTT) colorimetry and the relative growth rate (RGR) of the cells in each group was calculated; the cellular apoptosis in each group was detected by Hoechst staining.Results The sequence of sFlt-1(2-4) gene was equal to 915 base pair (bp).The transfection rate was 45% in nanoparticle group and 21% in lipofectamine group; the difference between the two groups was significant (t=2.541，Plt;0.05). Forty-eight hours after the transfection, the expression of sFlt-1（2-4）mRNA and protein was obviously higher in nanoparticle group than that in lipofectamine group (t=2.454，2.398；Plt;0.05) . Twenty-four and 48 hours after the transfection,the difference of RGR of the cells between nanoparticle and non-transfected group was not significant（t=1.436，Pgt;0.05）; the RGR in lipofectamine group differed much from that in non-transfected and nanoparticle group (t=2.412，2.545; Plt;0.05) ; the difference of cellular apoptosis was not significant between nanoparticle and nontransfected group (t=1.436，Pgt;0.05), but significant between nanoparticle and lipofectamine group (t=2.236，Plt;0.05). Conclusion The transfection rate of sFlt-1(2-4) mediated by carboxymethylated dextran coated nanoparticle was higher than that mediated by lipofectamineTM2000.