• Journal of Korean Neurosurgical Society
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• v.57 no.2
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• pp.77-81
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• 2015

Objective : The purpose of this study was to investigate changes in the plasma level of vascular endothelial growth factor (VEGF) after Gamma Knife radiosurgery (GKRS) for the treatment of meningioma. Methods : Fourteen patients with meningiomas had peripheral venous blood collected at the time of GKRS and at 1 week, 1 month, 3 month and 6 month visits. Plasma VEGF levels were measured using commercially available enzyme-linked immunosorbent assay. For controls, peripheral blood samples were obtained from 20 healthy volunteers. Results : The mean plasma VEGF level (29.6 pg/mL) in patients with meningiomas before GKRS was significantly lower than that of the control group (62.4 pg/mL, p=0.019). At 1 week after GKRS, the mean plasma VEGF levels decreased to 23.4 pg/mL, and dropped to 13.9 pg/mL at 1 month, 14.8 pg/mL at 3 months, then increased to 27.7 pg/mL at 6 months. Two patients (14.3%) with peritumoral edema (PTE) showed a level of VEGF 6 months after GKRS higher than their preradiosurgical level. There was no significant association found in an analysis of correlation between PTE and tumor size, marginal dose, age, and sex. Conclusion : Our study is first in demonstrating changes of plasma VEGF after stereotactic radiosurgery (SRS) for meningioma. This study may provide a stimulus for more work related to whether measurement of plasma level has a correlation with tumor response after SRS for meningioma.

• Journal of Acupuncture Research
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• v.24 no.5
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• pp.23-32
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• 2007

Objectives : Angiogenesis consists of the proliferation, migration, and differentiation of endothelial cells, and angiogenic factors and matrix protein interactions modulate this process. The aim of this study was to determine whether herbs medicine(KHBJs) could induce angiogenic activity in human umbilical vein endothelial cells(HUVECs). Methods : The angiogenic activity of KHBJs were evaluated by proliferation using BrdU assay, chemotactic migration assay, tube formation assay, and measurement of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor(VEGF) in HUVECs. Also, In order to identify enhance angiogenic activity by activity guided fractionation, the angiogenic activity of fractions of KHBJs such as KHBJB or KHBJR were evaluated in vitro and in vivo Matrigel plug angiogenesis asaay. Results : About 9 KHBJs significantly increased HUVECs proliferation in a dose-dependent manner. In addition, 9 herbs medicine(KHBJs) increased migration and tube-like formation in HUVECs. Interestingly the expression of bFGF and VEGF, an angiogenesis-inducing growth factor, were dose-dependently increased by KHBJs. However, angiogenic activity of fractionated KHBJs(KHBJB or KHBJR) not enhanced more than KHBJs in HUVECs and Matrigel plug in vivo angiogenesis assay. Conclusions : 9 KHBJs significantly induces angiogenesis in in vitro and in vivo. These results suggest that 9 KHBJs potent angiogenic agents and promising drug for the induction of neovascularization.

• BMB Reports
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• v.50 no.4
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• pp.208-213
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• 2017

Vascular endothelial growth factor (VEGF) is an essential cytokine that has functions in the formation of new blood vessels and regression of cardiac hypertrophy. VEGF/VEGF-receptor-1 (VEGFR1) signaling plays a key role in the regression of cardiac hypertrophy, whereas VEGF/VEGFR2 signaling leads to cardiac hypertrophy. In this study, we identified the prohypertrophic role of miR-374 using neonatal rat ventricular myocytes (NRVMs). Our results showed that overexpression of miR-374 activated G protein-coupled receptor-mediated prohypertrophic pathways by the inhibition of VEGFR1-dependent regression pathways. Luciferase assays revealed that miR-374 could directly target the 3'-untranslated regions of VEGFR1 and cGMP-dependent protein kinase-1. Collectively, these findings demonstrated that miR-374 was a novel pro-hypertrophic microRNA functioning to suppress the VEGFR1-mediated regression pathway.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.3
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• pp.1059-1063
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• 2012

Objective: Angiogenesis represents a key element in the pathogenesis of malignancy. There are no robust data on prognostic factors for overall survival (OS) in patients with metastatic colorectal cancer treated with vascular endothelial growth factor (VEGF)-targeted therapy. The present study was conducted to establish a prognostic model for patients using an oxaliplatin-based or irinotecan-based chemotherapy plus bevacizumab in metastatic colorectal cancer. Methods: Baseline characteristics and outcomes on 170 patients treated with FOLFIRI or XELOX plus anti-VEGF therapy-naive metastatic colorectal cancer were collected from three Turkey cancer centers. Cox proportional hazards regression was used to identify independent prognostic factors for OS. Results: The median OS for the whole cohort was 19 months (95% CI, 14.3 to 23.6 months). Three of the seven adverse prognostic factors according to the Anatolian Society of Medical Oncology (ASMO) were independent predictors of short survival: serum lactate dehydrogenase (LDH) greater than the upper limit of normal (ULN; p<0.001); neutrophils greater than the ULN (p<0.0014); and progression free survival (PFS) less than 6 months (p =0.001). Conclusion: Serum LDH and neutrophil levels were the main prognostic factors in predicting survival, followed by PFS. This model validates incorporation of components of the ASMO model into patient care and clinical trials that use VEGF-targeting agents.

• Journal of Korean Neurosurgical Society
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• v.59 no.5
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• pp.442-448
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• 2016

Objective : Increased expression of angiogenic factors, such as vascular endothelial growth factor (VEGF), is associated with the pathogenesis of cerebral cavernous malformations (CCMs). The purpose of this study was to investigate plasma levels of VEGF in normal subjects and in patients with CCM and to evaluate change in these levels following stereotactic radiosurgery (SRS). Methods : Peripheral venous blood was collected from 6 patients with CCM before SRS using Gamma Knife and at the 1 week, 1 month, 3month, and 6 month follow-up visits. Plasma VEGF levels were measured using commercially available enzyme-linked immunosorbent assay kits. Peripheral blood samples were obtained from 10 healthy volunteers as controls. Results : Mean plasma VEGF level of 41.9 pg/mL (range, 11.7-114.9 pg/mL) in patients with CCM at baseline was higher than that of the healthy controls (29.3 pg/mL, range, 9.2-64.3 pg/mL), without significant differences between CCM patients and controls (p=0.828). Plasma VEGF level following SRS dropped to 24.6 pg/mL after 1 week, and decreased to 18.5 pg/mL after 1 month, then increased to 24.3 pg/mL after 3 months, and 32.6 pg/mL after 6 months. Two patients suffering from rebleeding after SRS showed a higher level of VEGF at 6 months after SRS than their pretreatment level. Conclusion : Plasma VEGF levels in patients with CCM were elevated over controls at baseline, and decreased from baseline to 1 month after SRS and increased further for up to 6 months. Theses results indicated that anti-angiogenic effect of SRS might play a role in the treatment of CCMs.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.645-649
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• 2013

Objective: The prognostic role of vascular endothelial growth factor (VEGF) in bladder cancer remains controversial. This meta-analysis aimed to explore any association between overexpression and survival outcomes. Methods: We systematically searched for studies investigating the relationships between VEGF expression and outcome of bladder cancer patients. Study quality was assessed using the Newcastle-Ottawa Scale. After careful review, survival data were extracted from eligible studies. A meta-analysis was performed to generate combined hazard ratios (HRs) for overall survival (OS), disease-free survival (DFS) and disease-specific survival (DSS). Results: A total of 1,285 patients from 11 studies were included in the analysis. Our results showed that tissue VEGF overexpression in patients with bladder cancer was associated with poor prognosis in terms of OS (HR, 1.843; 95% CI, 1.231-2.759; P = 0.003), DFS (HR, 1.498; 95% CI, 1.255-1.787; P = 0.000) and DSS (HR, 1.562; 95% CI, 0.996-1.00; P = 0.052), though the difference for DSS was not statistically significant. In addition, there was no evidence of publication bias as suggested by Begg's and Egger's tests except for DFS (Begg's test, P = 0.221; Egger's test, P = 0.018). Conclusion: The present meta-analysis indicated elevated VEGF expression to be associated with a poor prognosis in patients with bladder cancer.

• Journal of Microbiology and Biotechnology
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• v.25 no.8
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• pp.1227-1233
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• 2015

Vascular endothelial growth factor (VEGF) plays a key role in angiogenesis through binding to its specific receptors, which mainly occurs to VEGF receptor 2 (VEGFR-2), a kinase insert domain-containing receptor. Therefore, the disruption of VEGFR-2 signaling provides a promising therapeutic approach for the treatment of cancer by inhibiting abnormal or tumorinduced angiogenesis. To explore this potential, we expressed the catalytic domain of VEGFR-2 (VEGFR-2-CD) as a soluble active kinase in Escherichia coli. The recombinant protein was purified and the VEGFR-2-CD activity was investigated. The obtained VEGFR-2-CD showed autophosphorylation activity and phosphate transfer activity comparable to the commercial enzyme. Furthermore, the IC₅₀ value of known VEGFR-2 inhibitor was determined using the purified VEGFR-2-CD. These results indicated a possibility for functional and economical VEGFR-2-CD expression in E. coli to use for inhibitor screening.

• Journal of Microbiology and Biotechnology
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• v.12 no.4
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• pp.702-705
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• 2002

Apicularen A (Api A) was recently isolated from Chondromyces sp. as a potent antitumor agent. Because of its unique chemical structure, a macrolide with a highly unsaturated amide side chain, and potent growth inhibitory effect in various cancer cell lines, Api A is currently in clinical trial for cancer therapy. In the present study, the effect of Api A on in vitro angiogenesis of bovine aortic endothelial cells (BAECS) was investigated. Api A potently inhibited the proliferation of BAECS in a dose-dependent manner. Treatment of the endothelial cells with up to 10 ng/ml of the compound did not show any cytotoxicity. In addition, it inhibited basic fibroblast growth factor (bFGF)-induced invasion and capillary tube formation of BAECS at concentrations of 2-5 ng/ml. These results, therefore, demonstrate that Apl A is a novel antiangiogenic agent and may suppress the growth of tumors, at least in part, by the inhibition of neovascularization.

• Molecules and Cells
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• v.22 no.3
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• pp.291-299
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• 2006

Vitexin, a natural flavonoid compound identified as apigenin-8-C-${\beta}$-D-glucopyranoside, has been reported to exhibit antioxidative and anti-inflammatory properties. In this study, we investigated its effect on hypoxiainducible factor-$1{\alpha}$ (HIF-$1{\alpha}$) in rat pheochromacytoma (PC12), human osteosarcoma (HOS) and human hepatoma (HepG2) cells. Vitexin inhibited HIF-$1{\alpha}$ in PC12 cells, but not in HOS or HepG2 cells. In addition, it diminished the mRNA levels of hypoxia-inducible genes such as vascular endothelial growth factor (VEGF), smad3, aldolase A, enolase 1, and collagen type III in the PC12 cells. We found that vitexin inhibited the migration of PC12 cells as well as their invasion rates, and it also inhibited tube formation by human umbilical vein endothelium cells (HUVECs). Interestingly, vitexin inhibited the hypoxia-induced activation of c-jun N-terminal kinase (JNK), but not of extracellular-signal regulated protein kinase (ERK), implying that it acts in part via the JNK pathway. Overall, these results suggest the potential use of vitexin as a treatment for diseases such as cancer.

• Journal of Life Science
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• v.16 no.7 s.80
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• pp.1199-1206
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• 2006

Plasminogen kringle 5 is a potent inhibitor of endothelial tell proliferation like an endogenous angiogenesis inhibitor, angiostatin consisting of plasminogen kringles 1-4. In this study, we produced the recombinant protein of plasminogen kringle 5 (PK5) employing an Pichia expression system and examined its. effect on~endothelial cell migration and its possible inhibitory mechanism. PK5 was expressed in Pichia pastoris GS115 by fusion of the cDNA spanning from Thr456 to Phe546 to the secretion signal sequence of a-factor prepro-peptide. After methanol induction, the secreted PK5 was purified by using S-spin column. SDS-PACE analysis of the purified protein showed one major band of approximately 10kDa. In in vitro migration assays, the purified protein inhibited dose-dependently the migration of human umbilical endothelial cells (HUVECs) induced by basic fibroblast growth factor (bFGF) or vascular endothelial growth factor (VEGF) with an $IC_{50}$ of approximately 500nM. Accordingly, it inhibited bfGF-stimulated extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation in HUVECs at 500nM. In addition, it also potently inhibited bFGF-induced cytoskeletal rearrangement of HUVECs. Thus, these results suggest that Pichia-produced PK5 effectively inhibits endothelial cell migration, in part by suppression of ERK1/2 activation and blocking cytoskeleton rearrangement.