Progress in The Study of VEGFR-2 Signaling Pathway / 生物化学与生物物理进展

Angiogenesis is of great importance to a variety of normal physiological processes and pathological disorders.It is tightly regulated by many mechanisms, among which vascular endothelial growth factor(VEGF) is one of the most potent promoters.VEGF binds and activates its specific receptor tyrosine kinases, especially vascular endothelial growth factor receptor-2(VEGFR-2).VEGFR-2 mediates the key functional and biochemical effects of VEGF in endothelial cells including proliferation, migration, survival, and permeability.Following its binding to VEGF, VEGFR-2 dimerizes and undergoes autophosphorylation on tyrosine residues within its cytoplasmic portion.This creates docking sites for adapter molecules to be recruited through their Src homology domain-2(SH2).These adapter molecules can then initiate the activation of downstream signaling cascades.Further down-stream effector molecules are activated, and regulate the biological effects of endothelial cells.It is also foound that VEGF/VEGFR-2 signaling pathway may negatively regulate the function of human monocyte-derived mature dendritic cells(DCs) as well as the maturation of immature-DCs.Advances in the understanding of the VEGF/VEGFR-2 signaling pathway may contribute to the discovery of kinds of pharmaceutical agents.

The Expression of Vascular Endothelial Growth Factor (VEGF)in Aplastic Anemia / 대한혈액학회지

BACKGROUND: Vascular endothelial growth factor (VEGF) is a potent angiogenic peptide with biologic effects that include regulation of hematopoietic stem cell development, extracellular matrix remodeling, and inflammatory cytokine generation. VEGF plasma levels are elevated in circulation during tumor growth and bone marrow proliferative status. In this study, to investigate the role of VEGF expression in patients with aplastic anemia (AA), VEGF protein expression and microvessel density (MVD) were evaluated. METHODS: Immunohistochemical staining for detecting VEGF protein was performed by the labeled avidin-biotin method on the formalin-fixed and paraffin embedded bone marrow biopsy samples of 25 patients with severe AA and 10 normal controls. Microvessels were scored in at least 3 areas (x200 fields) of the highest MVD in representative sections of each bone marrow biopsy specimen using immunohistochemistry for CD34 antigen. RESULTS: In AA, megakaryocytes and histiocytes expressed less intense cytoplasmic VEGF than in control (P < 0.05). However, plasma cells had higher VEGF immunoreactivity in AA than in control. MVD was significantly lower in patients with AA (21.43+/-7.24), compared to controls (27.65+/-3.44) (P < 0.05). MVD had a strong correlation with bone marrow cellularity. Also, the degree of VEGF immunoreactivity was correlated with bone marrow cellularity and MVD. CONCLUSION: Angiogenesis as assessed by MVD and VEGF expression seems to have a role in the pathogenesis of AA.

The Effect of Vascular Endothelial Growth Factor on Vascularization in Porous Polyethylene Orbital Implant (Medpor(R))

PURPOSE: We investigated the effect of VEGF usage and the method of surgery on the vascularization rate of the porous orbital implant (Medpor(R)). METHODS: Thirty six Newzealand white rabbits were randomized into 2 groups according to the method of surgery (evisceration and intrascleral implantation and evisceration and retroscleral implantation). Each group was subdivided into two groups, a group treated with VEGF, and the other without VEGF treatment. The degree of vascularization was observed in the four groups at 1, 2, 4 weeks by using cryofilm transfer kit (Finetec, Tokyo, Japan). The implant was sliced at the equator with cryomicrotome and stained with Hematoxylin and Eosin, Masson's trichrome and reticulin. The sample was observed to assay the degree of fibrovascular ingrowth with light microscope. RESULTS: The group in which VEGF was used and the implant was inserted retrosclerally (n=9) showed significantly higher vascularization rate than the other three groups (P0.05). CONCLUSIONS: After using VEGF or inserting the implant retrosclerally, the vascularization of the implant was significantly incresed.

Vascular Endothelial Growth Factor (VEGF) Expression and Angiogenesis in Gastric Cancer

PURPOSE: This study was designed to evaluate the angiogenic activities of gastric cancer tissue and adjacent normal gastric tissue and to analyze the correlations between the clinicopatholoic factors of gastric cancer and tumor angiogenic activity. METHODS: Sets of both tumor tissue and adjacent normal gastric tissue were sampled from 49 patients with gastric cancer at the time of gastrectomy. Each specimen was evaluated for the expression of VEGF mRNA by reverse transcriptase polymerase chain reaction (RT-PCR). For the microvessel count of each tissue sample, immunohistochemical staining was done using antiCD31 antibody. As a control group, 10 paraffin blocks of normal gastric tissue from patients with benign disease were selected and stained with the same antibody in order to count the microvessels. RESULTS: The microvessel count of the tumor tissue was higher than that of normal tissue, with a mean+/-SD of 74.10+/-30.33 and 24.69+/-10.11, respectively (p<0.001). The microvessel count of the control group was 23.40+/-6.77 and was not significantly different from that of normal tissue samples taken from patients with gastic cancer. VEGF/beta actin ratios measured from the results of RT-PCR were 0.70+/-0.32 in tumor tissue and 0.51+/-0.26 in normal tissue (p<0.001). In each tissue sample, there was a significant correlation between the microvessel count and VEGF/beta actin ratio (p<0.01 in the tumor tissue, p<0.05 in normal tissue). Micro-vessel count of tumor tissue was related with sex and types of Lauren's classification (p<0.05, p<0.01, respectively). The VEGF/beta actin ratio of tumor tissue was related to sex and degree of vascular invasion of tumor cells (p<0.05). Other clinicopathologic factors, such as age, histologic type, TNM stage, tumor depth, lymph node metastasis, and perineural invasion, were not associated with the degree of microvessel count and the level of VEGF mRNA expression. CONCLUSION: Gastric cancer shows marked angiogenic activity and the angiogenesis is related to some clinicopathologic factors. These results suggest that the clinical application of antiangiogenic agents may have a role in the treatment of gastric cancer.