• Clinical and Experimental Pediatrics
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• v.46 no.2
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• pp.167-172
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• 2003

Purpose : Pulmonary vascular hypertension is a common problem in congenital heart disease, the most common cardiac condition in childhood. However, the mechanisms responsible for this pathologic change, treatment, and prevention are poorly understood. Therefore, we studied the gene expression of vascular endothelial growth factor(VEGF) by using a hypoxic model of the pulmonary artery smooth muscle cells. Methods : The main pulmonary artery and its proximal branches of a 6 wk old Fischer rat were excised. They were cut into multiple small pieces and suspended in DMEM medium supplemented with 20% fetal bovine serum and incubated in 5% $CO_2$-95% air atmosphere. The smooth muscle cells were confirmed by immunostaining with smooth muscle myosin and ${\alpha}$-smooth muscle actin antibodies. The VEGF gene expression in the hypoxic group was compared with the one in control the group as well as the one in the starved group by RT-PCR and Northern blot hybridization. Results : There was no statistically significant difference among the control, hypoxic and starved groups. Conclusion : There are few studies of pulmonary vascular hypertension at the molecular level in Korea. Therefore, we studied the expression of VEGF gene in hypoxic pulmonary vascular smooth muscle cells. Further studies will be needed to find the difference between newly born and adult rats, or human and rat pulmonary vascular smooth muscle cells in gene expression. We hope that the study will lead to a better understanding of pulmonary vascular hypertension.

• Preventive Nutrition and Food Science
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• v.19 no.4
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• pp.299-306
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• 2014

Hesperetin has been shown to possess a potential anti-angiogenic effect, including vascular formation by endothelial cells. However, the mechanisms underlying the potential anti-angiogenic activity of hesperetin are not fully understood. In the present study, we evaluated whether hesperetin has anti-angiogenic effects in human umbilical vascular endothelial cells (HUVECs). HUVECs were treated with 50 ng/mL vascular endothelial growth factor (VEGF) to induce proliferation as well as vascular formation, followed by treatment with several doses of hesperetin (25, 50, and $100{\mu}M$) for 24 h. Cell proliferation and vascular formation were analyzed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and tube formation assay, respectively. In addition, cell signaling related to cell proliferation and vascular formation was analyzed by western blot. Furthermore, a mouse aorta ring assay was performed to confirm the effect of hesperetin on vascular formation. Hesperetin treatment did not cause differences in HUVECs proliferation. However, hesperetin significantly inhibited VEGF-induced cell migration and tube formation of HUVECs (P<0.05). Moreover, hesperetin suppressed the expression of ERK, p38 MAPK, and PI3K/AKT in the VEGF-induced HUVECs. In an ex vivo model, hesperetin also suppressed microvessel sprouting of mouse aortic rings. Taken together, the findings suggest that hesperetin inhibited vascular formation by endothelial cells via the inhibition of the PI3K/AKT, ERK and p38 MAPK signaling.

• Korean Journal of Environmental Biology
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• v.28 no.1
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• pp.14-19
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• 2010

Angiogenesis is an important event involved in cell growth and wound healing process. However, the imbalance of growth factors causes diseases, such as ocular, inflammatory diseases. One of treatment of these diseases is to suppress the formation of blood vessels. Function and mechanism of gold nanoparticles (AuNPs) in the formation of blood vessels is not yet proved. Pigment epithelium derived factor (PEDF) is currently being offered anti-angiogenic materials. In this study, we postulated that AuNPs might have the ability to inhibit angiogenesis, the pivotal step in tumor growth, invasion and metastasis. We have demonstrated that AuNPs could inhibit vascular endothelial growth factor (VEGF) induced cell proliferation, angiogenesis in bovine retinal endothelial cells.

• Journal of Korean Neurosurgical Society
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• v.29 no.10
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• pp.1303-1308
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• 2000

Objectives : It has been known that vascular endothelial growth factor(VEGF), as an endothelial cell-specific mitogen, induces angiogenesis, and possesses vascular permeability and procoagulant properties. Peritumoral brain edema(PTBE) is a common accompaniment of malignant gliomas. It results from microvascular extravasation of plasma and proteins through the interendothelial spaces. The correlation between pathological grading, PTBE, neovascularization, and the expression of VEGF were analyzed in 31 patients with astrocytic tumors. Methods : Astrocytic tumor samples(8 astrocytomas, 14 anaplastic astrocytomas, and 9 glioblastomas) from 31 patients( 21 males and 10 females : average age $37{\pm}24$ years) who underwent surgery were examined retrospectively for the expression of VEGF and CD31(microvasculature) immunohistochemically. The extent of PTBE was examined by using preoperative CT or MRI as an edema index(EI). In addition to VEGF and CD31, several causative factors including tumor size, histologic type were compared with EI. Results : Only one of 8 astrocytomas, and majority of high grade(21 of 23 anaplastic astrocytomas and glioblastomas) tumors demonstrated PTBE(p<0.05). The majority of high grade tumors showed higher expression of VEGF (p<0.01). High grade tumors showed even higher CD31 expression(p<0.05), however, there was no close correlation between expression of VEGF and CD31. The EI was increased significantly, just as VEGF(p<0.01), but CD31 expression was not correlated with high EI. Conclusion : These data suggest that VEGF expression is closely correlated with PTBE and histological grading in astrocytic tumors. Microvasculature(CD31) in tumors is highly correlated with histological grading, however, shows no correlation with the expression of VEGF and PTBE.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.42
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• pp.23.1-23.11
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• 2020

Background: 4-Hexylresorcinol (4HR) is able to increase angiogenesis. However, its molecular mechanism in the human endothelial cells has not been clarified. Methods: As endothelial cells are important in angiogenesis, we treated the human umbilical vein endothelial cells (HUVECs) with 4HR and investigated protein expressional changes by immunoprecipitation high-performance liquid chromatography (IP-HPLC) using 96 antisera. Results: Here, we found that 4HR upregulated transforming growth factor-β (TGF-β)/SMAD/vascular endothelial growth factor (VEGF) signaling, RAF-B/ERK and p38 signaling, and M2 macrophage polarization pathways. 4HR also increased expression of caspases and subsequent cellular apoptosis. Mechanistically, 4HR increased TGF-β1 production and subsequent activation of SMADs/VEGFs, RAF-B/ERK and p38 signaling, and M2 macrophage polarization. Conclusion: Collectively, 4HR activates TGF-β/SMAD/VEGF signaling in endothelial cells and induced vascular regeneration and remodeling for wound healing.

• Clinical and Experimental Reproductive Medicine
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• v.31 no.4
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• pp.235-244
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• 2004

Objective: The effects on spermatogenesis by expression of vascular endothelial growth factor (VEGF) and endothelin-1 (ET-1) were investigated. Materials and Methods: Testicular specimens were obtained from 40 infertile males due to primary testicular failure and from 10 fertile males with other urologic problems. The specimens of infertile males were devided into 4 groups according to histologic findings; Sertoli cell only syndrome (A), maturation arrest (B), hypospermatogenesis (C) and sloughing and disorganization (D). VEGF and ET-1 expression were detected with immunohistochemical stain. Results: VEGF expression on Leydig cell was detected in all cases. But, VEGF expression rates on germ cell were significantly higher in infertile group B, C, D compared to that of the control group (p<0.05). ET-1 expression rates on Leydig cell was significantly lower in all infertile group compared to that of the control group (p<0.05). But, ET-1 expression rates on Sertoli cell was significantly higher in all infertile group compared to that of the control group (p>0.05). In germ cell of infertile group, LH, FSH and prolactin were significantly decreased, and estradiol is increased in positive stain group on ET-1 immunohistochemical stain (p<0.05). VEGF and ET-1 expression were not correlated mean seminiferous tubule diameter (p>0.05). Conclusions: Abnormal spermatogenesis would be reflected in VEGF expression in germ cell.

• BMB Reports
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• v.40 no.3
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• pp.439-443
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• 2007

Tumor growth and metastasis are dependent on angiogenesis, and endothelial cell invasion and migration are apparent means of regulating tumor progression. We report here that saxatilin, a snake venom-derived disintegrin, suppresses the angiogenesis-inducing properties of NCI-H460 human lung cancer cells. Culture supernatants of NCI-H460 cells are able to induce human umbilical vascular endothelial cell (HUVEC) invasion and tube formation. However, treatment of the cancer cells with saxatilin resulted in reduced angiogenic activity of the culture supernatant. This suppressed angiogenic property was found to be associated with the level of vascular endothelial growth factor (VEGF) in the culture supernatant. Further experimental evidence indicated that saxatilin inhibits VEGF production in NCI-H460 cells by affecting hypoxia induced factor-1$\alpha$ (HIF-1$\alpha$) expression via the Akt pathway.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.337.2-337.2
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• 2002

Conjugated linoleic acid (CLA) is a potent inhibitor of mammary carcinogenesis. Cancer cells produce various angiogenic factors which stimulate host vascular endothelial cell mitogenesis and chemotaxis for their growth and metastasis. Basic fibroblast growth factor (bFGF) is a potent angiogenic factor that is expressed in many tumors. In this study. we found that CLA decreased bFGF-induced endothelial cell proliferation and DNA synthesis in a dose-dependent manner. However, CLA did not inhibit endothelial cell migration. Furthermore CLA showed a potent inhibitory effect on embryonic vasculogenesis and bF GF-induced angiogenesis in vivo. Collectively. these results suggest that CLA selectively inhibis the active proliferating endothelial edll induced by bFGF. which may explain its anti-carcinogenix properties in vivo.

• Biomolecules & Therapeutics
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• v.31 no.4
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• pp.456-465
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• 2023

Cervical tumors represent a prevalent form of cancer affecting women worldwide; current treatment options involve surgery, radiotherapy, and chemotherapy. Angiogenesis, the process of new blood vessel formation, is a crucial factor in cervical tumor growth. The molecular mechanisms underlying the effects of the liver kinase B1 (LKB1/STK11) tumor suppressor protein on tumor angiogenesis have not been elucidated. Therefore, we investigated the role of LKB1 in cervical tumor angiogenesis both in vitro and in vivo in this study. Our results demonstrated that LKB1 inhibited cervical tumor angiogenesis by suppressing the expression of angiogenesis-related factors such as vascular endothelial growth factor (VEGF) and hypoxia inducible factor-1α. LKB1 directly affected both carcinoma and vascular endothelial cells, resulting in a significant reduction in tumor growth and angiogenesis. Furthermore, LKB1 was found to bind to VEGF receptor 2 (VEGFR-2) and target the VEGFR-2-mediated protein kinase B/mechanistic target of rapamycin signaling pathway in endothelial cells, thereby reducing cervical tumor growth and angiogenesis. Our study provides new insights into the molecular mechanisms underlying the anti-tumor and anti-angiogenic effects of LKB1 in cervical cancer. These findings will help develop new therapeutic strategies for cervical cancer.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.31 no.1
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• pp.27-34
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• 2009

Angiogenesis is essential for solid tumor growth and progression. Among the pro-angiogenetic factors, vascular endothelial growth factor(VEGF), also known as vascular permeability factor, is the most important as a mitogen for vascular endothelium. The VEGF family of molecules currently consists of six growth factors, VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-E, and placenta growth factor(PlGF). Over-expression of PlGF is associated with angiogenesis under pathological conditions such as ischemia, inflammation, and cancer. Hence, the goal of this study is to identify the correlation of clinicopathlogical factors and the up-regulation of PlGF expression in oral squamous cell carcinoma. We studied the immunohistochemical staining of PlGF, PlGF gene expression and a real time quantitative RT-PCR in 20 specimens of 20 patients with oral squamous cell carcinoma. The results were as follows. 1. In the immunohistochemical study of poorly differentiated and invasive oral squamous cell carcinoma, the high level staining of PlGF was observed. And the correlation between immunohistopathological PlGF expression and histological differentiation of specimens was significant (Pearson correlation analysis, significance [r] >0.6, P < .05). 2. In the PlGF gene RT-PCR analysis, PlGF expression was more in tumor tissue than in adjacent normal tissue. Paired-samples analysis determined the difference of PlGF mRNA expression level between the cancer tissue and the normal tissue (Student's t - test, P < .05) These findings suggest that up-regulation of the PlGF gene may play a role in progression and local metastasis in invasive oral squamous cell carcinoma.