• BMB Reports
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• v.49 no.3
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• pp.191-196
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• 2016

Vascular endothelial growth factor (VEGF) is a key mediator of angiogenesis and critical for normal embryonic development and repair of pathophysiological conditions in adults. Although phospholipase D (PLD) activity has been implicated in angiogenic processes, its role in VEGF signaling during angiogenesis in mammals is unclear. Here, we found that silencing of PLD2 by siRNA blocked VEGF-mediated signaling in immortalized human umbilical vein endothelial cells (iHUVECs). Also, VEGF-induced endothelial cell survival, proliferation, migration, and tube formation were inhibited by PLD2 silencing. Furthermore, while Pld2-knockout mice exhibited normal development, loss of PLD2 inhibited VEGF-mediated ex vivo angiogenesis. These findings suggest that PLD2 functions as a key mediator in the VEGF-mediated angiogenic functions of endothelial cells.

• Journal of Gastric Cancer
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• v.9 no.3
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• pp.96-103
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• 2009

Purpose: Lymph node metastasis is an important factor in determining prognosis and therapeutic options for early gastric cancer (EGC) patients. Vascular endothelial growth factor (VEGF)-C and D are known as lymphangiogenic factors, and cyclooxygenase (COX)-2 is thought to play a role in lymph node metastasis in gastric carcinoma. This study was designed to determine whether the expression of VEGF-C, VEGF-D, and COX-2 is associated with clinicopathologic factors, especially lymph node metastasis in EGCs invading the submucosa. Materials and Methods: Tissue samples were obtained from 85 Patients undergoing standard gastrectomy with lymph node dissection between 1991 and 2007 in the Department of Surgery of Daejeon St. Mary's Hospital in Daejeon, Korea. All patients were diagnosed with gastric cancers and submucosal invasion. We examined the expression of VEGF-C, VEGF-D, and COX-2 using immunohistochemical methods. Results: Of the 85 patients, 16 (18.8%) had lymph node metastasis. VEGF-C, VEGF-D, and COX-2 were positively expressed in 34.1% (29/85), 22.3% (19/85), and 37.6% (32/85) of the patients. VEGF-C and COX-2 expression was significantly correlated with lymph node metastasis (P<0.05). A positive correlation existed between VEGF-C and COX-2 expression (P< 0.001). Conclusion: VEGF-C and COX-2 expression is associated with lymph node metastasis in gastric cancer with submucosal invasion. VEGF-C and COX-2 may thus be predictive markers for lymph node metastasis in EGC patients with submucosal invasion.

• The korean journal of orthodontics
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• v.31 no.1 s.84
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• pp.121-136
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• 2001

This study was performed to analyse the expression of VEGF and it's receptor(VEGFR) in the tension side of the periodontal ligament following orthodontic tooth movement. Upper first molars of Sprague-Dawley rats were moved medially using closed coil spring for 1, 2, 24 hours and 3, 7, 14 days. H&E staining, immunohistochemical staining and in situ hybridization methods were used to analyse the change of the expression of VEGF and VEGFR. The results from this study were as follows : 1. Following tensional force, periodontal ligament showed elongation of fibers, compression and congestion of vessels and regional hemorrhage. These tissue changes were recovered within 3 days of force application. New bone formation was seen after 3 days of force application and continued for the remaining experimental periods. 2. Following tensional force, VEGF and VEGF mRNA expression was increased in the periodontal ligament cells, osteoblasts and cementoblasts. This change was followed by increased vasculature in the periodontal ligament. 3. After 3 days of tensional force, VEGF and VEGF mRNA expression was confined mainly to the osteopaths and the periodontal ligament cells adjacent to the alveolar bone. After 2 weeks of force application, VEGF and VEGF mRNA expression was reduced to the level of control sample. 4. VEGFRs(Flt-1, Flk-1) showed similar expression pattern and it's expression was mainly seen in the endothelial cells and osteoblasts. Following tensional force VEGFR expression was increased in the endothelial cells and osteoblasts. In conclusion, in the tension side of the penodontal ligament, ligament cells, osteoblast and cementoblast showed increased expression of VEGF & VEGF mRNA. It preceded the increase of vasculature and new bone formation. The increased expression of VEGF mRNA in cementoblast may induce periodontal vessels, which distribute mainly the bone side half of periodontal ligament, grow in the direction of tensional force. Increased expression of VEGFR & VEGFR mRNA not only in endothelial cell but in osteoblast, osteocyte and periodontal cells showed VEGF acts not only in paracrine manner but in autocrine one.

• Clinical and Experimental Pediatrics
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• v.48 no.8
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• pp.886-893
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• 2005

Purpose : Kawasaki disease is the most common cause of systemic vasculitis in children less than 5 years of age. Recent immunohistochemistry findings suggest that many vascular growth factors play a role in the formation of the coronary artery lesions. Active remodeling of the coronary artery lesions in Kawasaki disease continues in the form of intimal proliferation and neoangiogenesis for several years after the onset of the disease. Intravenous immunoglobulin(IVIG) and corticosteroid have been used in the treatment of Kawasaki disease but the exact mechanism is not clear. We have investigated that IVIG and corticosteroid inhibited vascular endothelial growth factor(VEGF)-induced tube formation of endothelial cells in vitro on Matrigel assay. Methods : Human umbilical vein endothelial cells(HUVECs) were cultured and seeded on Matrigel coated 24 well plates in medium with or without the following agents : VEGF, VEGF plus IVIG, VEGF plus VEGF antibody, VEGF plus methylprednisolone, VEGF, IVIG plus methylprednisolone for 18 hours. The total length of tube structures in each photograph was quantified. Results : IVIG significantly inhibited the proliferation of HUVECs. The inhibitory effect of IVIG was also reversible. In the meantime, VEGF induced the differentiation of HUVECs into capillary like structures on Matrigel, which was inhibited by VEGF antibody in a dose-dependent manner. Interestingly, IVIG and methylprednisolone inhibited VEGF-induced tube formation of HUVECs. IVIG was more effective in inhibition than methylprednisolone alone. Conclusion : We revealed that VEGF induced the differentiation of HUVECs and this effect was inhibited by IVIG and methylprednisolone.

• Tuberculosis and Respiratory Diseases
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• v.64 no.3
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• pp.200-205
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• 2008

Background: Tumor angiogenesis plays an important role in tumor growth, maintenance and metastatic potential. Tumor tissue produces many types of angiogenic growth factors. Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) have both been implicated to have roles in tumor angiogenesis. In this study, the expression of tissue VEGF and bFGF from non-small cell lung cancer (NSCLC) patients were analyzed. Methods: We retrospectively investigated 35 patients with a histologically confirmed adenocarcinoma or squamous cell carcinoma of the lung, where the primary curative approach was surgery. An ELISA was employed to determine the expression of VEGF and bFGF in extracts prepared from 35 frozen tissue samples taken from the cancer patients. Results: VEGF and bFGF concentrations were significantly increased in lung cancer tissue as compared with control (non-cancerous) tissue. The VEGF concentration was significantly increased in T2 and T3 cancers as compared with T1 cancer. Expression of VEGF was increased in node-positive lung cancer tissue as compared with node-negative lung cancer tissue (p=0.06). VEGF and bFGF expression were not directly related to the stage of lung cancer and patient survival. Conclusion: Expression of VEGF and bFGF were increased in lung cancer tissue, and the expression of VEGF concentration in lung cancer tissue was more likely related with tumor size and the presence of a lymph node metastasis than the expression of bFGF. However, in this study, expression of both VEGF and bFGF in tissue were not associated with patient prognosis.

• Clinical and Experimental Pediatrics
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• v.46 no.8
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• pp.811-816
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• 2003

Purpose : Kawasaki disease is an acute systemic vasculitis of unknown etiology with a predilection for the coronary arteries. Vascular endothelial growth factor(VEGF) is a cytokine which promotes vascular permeability and angiogenesis. We investigated serum VEGF(sVEGF) levels in Kawasaki disease to determine whether sVEGF level can be used as a risk factor to predict the occurrence of coronary artery lesions(CAL) in Kawasaki disease. Methods : We measured sVEGF levels in 11 patients with Kawasaki disease in acute phase(patient group)and 11 normal children(control group) by enzyme-linked immunosorbent assay(ELISA) method. We investigated the relationship between sVEGF levels and the lumen diameters of coronary artery and other potential CAL risk factors; duration of fever, hemoglobin, WBC counts, platelet counts, ESR, CRP and LDH levels. Results : SVEGF levels of patients in the acute phase of Kawasaki disease(mean $847.9{\pm}495.7pg/mL$) were significantly higher than that of normal controls(mean $279.9{\pm}150.6pg/mL$; P<0.05). SVEGF levels showed significant positive correlation with the lumen diameters of the coronary artery(P<0.05, $r_s=0.75$) in the patient group. There was no significant correlation between sVEGF levels and duration of fever or other laboratory measurements. Conclusion : Our results support the notion that sVEGF level may be considered as a predictive indicator for the occurrence of coronary artery lesions in Kawasaki disease.

• Korean Journal of Head & Neck Oncology
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• v.18 no.1
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• pp.23-29
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• 2002

Mutation of the P53 tumor suppressor gene playa major role in the development of many carcinomas, namely in the colon, breast and bladder, whereas the role played by such mutations in thyroid carcinogenesis remains controversial. Vascular endothelial growth factor (VEGF) induces proliferation of endothelial cells, stimulates angiogenesis, and increases vascular permeability. Increased VEGF expression has been associated with poor clinical outcomes in many malignancies E-cadherin, a calcium-dependent transmembrane glycoprotein, is an adhesion molecule Expression of p53, VEGF and E-cadherin was assessed immunohistochemically in 19 tall columnar variant of papillary carcinoma, 24 common papillary carcinoma and 7 follicular carcinoma. The aim of this study was to evaluate the expression of P53,VEGF and E-cadherin as a potential maker for the prognosis of thyroid carcinomas. The results are as follows: 1) There were no significance in any clinical parameters examined among tall columnar variant of papillary carcinoma, common papillary carcinoma and follicular carcinoma. 2) The expression of P53 demonstrated low in tall columnar variant of papillary carcinoma, common papillary carcinoma and follicular carcinoma, but a significantly high in regional lymph node metastasis. 3) The expression of VEGF demonstrated a significantly high in regional lymph node metastasis than those without metastasis in papillary thyroid carcinoma. 4) The expression of E-cadherin demonstrated less often among papillary carcinomas with lymph node metastasis than in those without metastasis in papillary thyroid carcinoma. In conclusion, it is suggested that VEGF and E-cadherin will be useful for the diagnosis of thyroid carcinoma and serves as a biological marker for thyroid carcinoma lymph node metastasis.

• Archives of Reconstructive Microsurgery
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• v.13 no.2
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• pp.101-106
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• 2004

Purpose : This study evaluated the effect of VEGF in the arterial anastomosis by using light and electron microscopy. Marerials and method : Rats underwent femoral arterial end-to-end anastomosis after transection and topical VEGF treatment. The proximal and distal segments of the femoral arteries was drenched with 1 drop of VEGF $(100ng/100{\mu}l/bottle)$. and when half of the repair was finished, the other 1 drop was drenched and then the repair was continued to complete the anastomosis. Gross and histologic characteristics of arterial wall were assessed after 3 days, 1, 3 and 5 weeks. In the control group, normal saline solution instead of VEGF was dropped with the same method in the anastomosis. Results : The histologic findings of the arterial wall were the vascular remodeling with the infiltration of inflammatory cells at early stages and the tissue fibrosis at lately stages in the anastomotic sites of the control and the VEGF-treated groups. The scanning electron microscopic results were; (1) the anastomotic sites were covered by many irregular cells with long cytoplasmic processes at the early stages. (2) After 1 week, endothelial cells started to cover the anastomotic sites. (3) After 3 weeks, the anastomotic sites were partially covered by endothelial cells in the control group. (4) After 5 weeks, the anastomotic sites were completely covered by endothelial cells in the control and VEGF-treated groups. (5) In the VEGF-treated group, the anastomotic site was completely covered by endothelial cells which directed parallel to longitudinal axis of arteries after 3 weeks. Conclusion : Topical VEGF maintained luminal integrity by decreasing fibrosis and increasing re-endothelialization. These findings suggest that topical VEGF may be a promising new strategy to enhance healing and improve the outcome of vascular anastomosis.

• IMMUNE NETWORK
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• v.10 no.2
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• pp.76-81
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• 2010

Ultraviolet B (UVB) induces multiple inflammatory and carcinogenic reactions. In skin, UVB induces to secrete several kinds of inflammatory cytokines from keratinocytes and also increases angiogenic process via the modulation of vascular endothelial growth factor (VEGF) production. Interleukin-21 (IL-21) is an inflammatory cytokine and produced by activated T cells. The biologic functions of IL-21 have not yet extensively studied. In the present study, we investigate the production of IL-21 from human keratinocyte cell line, HaCaT and its biological effect after exposure to UVB. First, we confirmed the IL-21 production and its receptor expression in HaCaT. And then, the change of IL-21 and VEGF production in HaCaT by UVB irradiation was examined. Not only IL-21 but also VEGF production was enhanced by UVB irradiation. Next, to determine relationship of enhanced production of IL-21 and VEGF, we detected VEGF production after neutralization of IL-21. VEGF production was reduced by IL-21 neutralization, which indicates that the IL-21 is involved in the VEGF production. Taken together, our results suggest that IL-21 and VEGF production is enhanced by UVB irradiation in HaCaT. In addition, it seems that IL-21 plays a role in the angiogenic process in skin via the modulation of VEGF production.

• Korean Journal of Head & Neck Oncology
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• v.21 no.2
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• pp.183-189
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• 2005

Objectives: Angiogenesis is the process of new blood vessel development from preexisting vessel. The growth of tumor is dependent on angiogenesis. This study was aimed to determine the role of the VEGF expression and MVD(microvessel density) in salivary gland tumors and to analyze the correlation between the expression of VEGF/MVD, and clinical manifestation. Material and Methods: We analyzed the expression of VEGF and average MVD and neo-MVD in the 57 cases of salivary gland tumors by immunohistochemistry. Results: VEGF expression was higher in malignant tumors than in benign tumors. Average and neo-MVD were not different in benign tumor and malignant tumor. There was a tendency of positive correlation between VEGF expression and MVD but it was not statistically significant. Stage, T stage and recurrance rate were not correlated with VEGF expression, average-MVD and neo-MVD. Expression of VEGF, average-MVD and neo-MVD were significantly increased in Warthin's tumor compared with pleomorphic adenoma. Conclusion: Overexpression of VEGF has an important role in malignant salivary gland tumors.