• The Journal of Korean Physical Therapy
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• v.14 no.1
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• pp.219-226
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• 2002

Vascular endothelial growth factors(VEGFs) constitute a group of structurally and functionally related growth factor that modulate many important physiological functions of endothelial cells, especially angiogenesis. This paper explain substance, which participate in signaling transduction of VEGF, including Bcl-2, caspase, focal adhesion kinase(FAK), integrin ${\alpha}v{\beta}3$, MAP kinase, nitric oxide(NO)and prostacyclin(PGI2). Physical therapy enhance angiogenesis for repairment of injury which as wound healing, muscle contusion, cerebrovascular disease, rheumatoid arthritis. Therefore this review assist understanding for mechanism of physical therapy as therapeutic angiogenesis.

• Biomolecules & Therapeutics
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• v.26 no.5
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• pp.474-480
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• 2018

Most angiogenesis assays are performed using endothelial cells. However, blood vessels are composed of two cell types: endothelial cells and pericytes. Thus, co-culture of two vascular cells should be employed to evaluate angiogenic properties. Here, we developed an in vitro 3-dimensional angiogenesis assay system using spheroids formed by two human vascular precursors: endothelial colony forming cells (ECFCs) and mesenchymal stem cells (MSCs). ECFCs, MSCs, or ECFCs+MSCs were cultured to form spheroids. Sprout formation from each spheroid was observed for 24 h by real-time cell recorder. Sprout number and length were higher in ECFC+MSC spheroids than ECFC-only spheroids. No sprouts were observed in MSC-only spheroids. Sprout formation by ECFC spheroids was increased by treatment with vascular endothelial growth factor (VEGF) or combination of VEGF and fibroblast growth factor-2 (FGF-2). Interestingly, there was no further increase in sprout formation by ECFC+MSC spheroids in response to VEGF or VEGF+FGF-2, suggesting that MSCs stimulate sprout formation by ECFCs. Immuno-fluorescent labeling technique revealed that MSCs surrounded ECFC-mediated sprout structures. We tested vatalanib, VEGF inhibitor, using ECFC and ECFC+MSC spheroids. Vatalanib significantly inhibited sprout formation in both spheroids. Of note, the $IC_{50}$ of vatalanib in ECFC+MSC spheroids at 24 h was $4.0{\pm}0.40{\mu}M$, which are more correlated with the data of previous animal studies when compared with ECFC spheroids ($0.2{\pm}0.03{\mu}M$). These results suggest that ECFC+MSC spheroids generate physiologically relevant sprout structures composed of two types of vascular cells, and will be an effective pre-clinical in vitro assay model to evaluate pro- or anti-angiogenic property.

• Animal Bioscience
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• v.34 no.4
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• pp.533-538
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• 2021

Objective: Pluripotent stem cell-derived lymphatic endothelial cells (LECs) show great promise in their therapeutic application in the field of regenerative medicine related to lymphatic vessels. We tested the approach of forced differentiation of mouse embryonal stem cells into LECs using biodegradable poly lactic-co-glycolic acid (PLGA) nanospheres in conjugation with growth factors (vascular endothelial growth factors [VEGF-A and VEGF-C]). Methods: We evaluated the practical use of heparin-conjugated PLGA nanoparticles (molecular weight ~15,000) in conjugation with VEGF-A/C, embryoid body (EB) formation, and LEC differentiation using immunofluorescence staining followed by quantification and quantitative real-time polymerase chain reaction analysis. Results: We showed that formation and differentiation of EB with VEGF-A/C-conjugated PLGA nanospheres, compared to direct supplementation of VEGF-A/C to the EB differentiation media, greatly improved yield of LYVE1(+) LECs. Our analyses revealed that the enhanced potential of LEC differentiation using VEGF-A/C-conjugated PLGA nanospheres was mediated by elevation of expression of the genes that are important for lymphatic vessel formation. Conclusion: Together, we not only established an improved protocol for LEC differentiation using PLGA nanospheres but also provided a platform technology for the mechanistic study of LEC development in mammals.

• Journal of Korean Neurosurgical Society
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• v.29 no.9
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• pp.1222-1227
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• 2000

Objective : Vascular endothelial growth factor(VEGF), an endothelial cell specific cytokine, is a potent angiogenic growth factor implicated in the tumor angiogenesis and increases vascular permeability dramatically. Peritumoral brain edema(PTBE) occurs in 40-60% of meningiomas. Many causative factors have been investigated, but the mechanism of PTBE associate with meningioma is unclear. VEGF has been implicated as one of the causative factors of PTBE. This study was designed to determine whether the extent of VEGF expression is correlated with degree of PTBE in meningiomas. Methods : Meningioma tissue samples from 40 patients(7 men and 33 women, mean age $53{\pm}13years$) who underwent surgery were examined retrospectively for the expression of VEGF immunohistochemically. The extent of PTBE was estimated by using preoperative CT or MRI as an edema index(EI). In addition to VEGF, several causative factors including tumor size, location, histologic type, microvasculature(CD31) were compared with EI. Results : Twenty-six meningiomas demonstrated PTBE, and the other 14 did not. Of the 40 patients of meningiomas, 28 were positive(17 were 1+ and 11 were 2+) for VEGF. The EI increased significantly just as VEGF was strongly expressed(p=0.006). Microvascular proliferation was also closely correlated with the extent of peritumoral brain edema(p<0.05). Conclusion : These data suggest that VEGF expression and microvascular proliferation are closely correlated with PTBE in meningioma.

• Genomics & Informatics
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• v.19 no.1
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• pp.6.1-6.10
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• 2021

Vascular endothelial growth factor (VEGF) is expressed at elevated levels by most cancer cells, which can stimulate vascular endothelial cell growth, survival, proliferation as well as trigger angiogenesis modulated by VEGF and VEGFR (a tyrosine kinase receptor) signaling. The angiogenic effects of the VEGF family are thought to be primarily mediated through the interaction of VEGF with VEGFR-2. Targeting this signaling molecule and its receptor is a novel approach for blocking angiogenesis. In recent years virtual high throughput screening has emerged as a widely accepted powerful technique in the identification of novel and diverse leads. The high resolution X-ray structure of VEGF has paved the way to introduce new small molecular inhibitors by structure-based virtual screening. In this study using different alkaloid molecules as potential novel inhibitors of VEGF, we proposed three alkaloid candidates for inhibiting VEGF and VEGFR mediated angiogenesis. As these three alkaloid compounds exhibited high scoring functions, which also highlights their high binding ability, it is evident that these alkaloids can be taken to further drug development pipelines for use as novel lead compounds to design new and effective drugs against cancer.

• International Journal of Stem Cells
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• v.17 no.1
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• pp.15-29
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• 2024

The development and differentiation of endothelial cells (ECs) are fundamental processes with significant implications for both health and disease. ECs, which are found in all organs and blood vessels, play a crucial role in facilitating nutrient and waste exchange and maintaining proper vessel function. Understanding the intricate signaling pathways involved in EC development holds great promise for enhancing vascularization, tissue engineering, and vascular regeneration. Hematopoietic stem cells originating from hemogenic ECs, give rise to diverse immune cell populations, and the interaction between ECs and immune cells is vital for maintaining vascular integrity and regulating immune responses. Dysregulation of vascular development pathways can lead to various diseases, including cancer, where tumor-specific ECs promote tumor growth through angiogenesis. Recent advancements in single-cell genomics and in vivo genetic labeling have shed light on EC development, plasticity, and heterogeneity, uncovering tissue-specific gene expression and crucial signaling pathways. This review explores the potential of ECs in various applications, presenting novel opportunities for advancing vascular medicine and treatment strategies.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.5
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• pp.1677-1682
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• 2015

Cancer progression is attained by uncontrolled cell division and metastasis. Increase in tumor size triggers different vascular channel formation to address cell nutritional demands. These channels are responsible for transferring of nutrients and gaseous to the cancer cells. Cancer vascularization is regulated by numerous factors including vascular endothelial growth factors (VEGFs). These factors play an important role during embryonic development. Members included in this group are VEGFA, VEGFB, VEGFC, PIGF and VEGFD which markedly influence cellular growth and apoptosis. Being freely diffusible these proteins act in both autocrine and paracrine fashions. In this review, genetic characterization these molecules and their putative role in cancer staging has been elaborated. Prognostic significance of these molecules along with different stages of cancer has also been summarized. Brief outline of ongoing efforts to target hot spot target sites against these VEGFs and their cognate limitations for therapeutic implications are also highlighted.

• Korean Journal of Head & Neck Oncology
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• v.20 no.2
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• pp.128-134
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• 2004

Background and Objectives: Angiogenesis is the process of new blood vessel development from preexisting vessel. Angiogenenesis has been considered to be essential for the growth and expansion of a solid tumor. Vascular endothelial growth factor (VEGF), known as one of the most important vascular permeability factors, induces proliferation of endothelial cells, stiumulates angiogenesis, and increases vascular permeability. Several recents reports have documented that VEGF overexpression is associated with poor clinical outcomes in many maligmancies. The aims of this study were to determine whether microvessel density and VEGF expression are related to clinicopathologic factors such as age, sex, tumor size, tumor stage, and prognostic factors and to evaluate the relationship between VEGF expression and angiogenesis in benign and malignant thyroid tumors. Materials and Methods: The subjects were 65 patients (27 with papillary carcinoma, 27 with adenomatous hyperplasia, 11 with follicular adenoma) who underwent thyroidectomy from 1995 to 2001. Imuunohistochemistry was used to detect VEGF expression and microvessel density (MVD) in paraffin-embedded thryoid tumor specimens. Results: The intensity of the VEGF expression did not show stastically difference between benign and malignant thyroid tumors. There was no apparent correlation between VEGF expression and age, tumor size, T stage or scores of the AGES, AMES and MACIS systems. The neo-microvessel density was higher in the maligant tumor than the benign tumors. Also, higher neo-microvessel density was associated with metastases of the lymph nodes and scores of the AMES and AGES systems. Conclusion: Our results suggest that neo-microvessel vessel density may be a significant prognostic factor in the thyroid papillary carcinoma. But the VEGF expression does not appear to be an significant independent prognostic factor for thyroid papillary carcinoma.

• Journal of Industrial Convergence
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• v.21 no.3
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• pp.171-179
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• 2023

To investigate the effects of type of exercise on inflammatory factor and vascular endothelial growth factor in middle aged women, we recruited 18 people middle-aged women and they divided into 3 groups (N=6, resistance exercise group, 40-60% of 1RM, N=6 aerobic exercise group, 60-70% of VO2max, N=6, flexibility exercise group, 10-60 sec/sets). The data were compared to the effect of exercise between 50 ~ 60 minutes per a day, 3 day times per week on the body composition, inflammatory factor, vascular endothelial growth factor and vascular compliance in middle aged women. First, in regards to inflammatory factors between groups, a significant difference (p<.05) was identified in the effects of CRP and IL-6 in terms of time (T). Second, regarding vascular endothelial growth factors between groups based on the type of exercise, a significant difference (p<.05) was found in the effects of VEGF's time (T) and the interaction between time and group (TxG). In conclusion, All types of exercise could partially improve inflammatory factors and vascular endothelial growth factors.

• 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.