• Physical Therapy Korea
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• v.13 no.2
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• pp.9-15
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• 2006

Skeletal muscle injury occurs frequently in sports medicine and is the most general form of injury followed by physical impact. There are growth factors which conduct proliferation, differentiation, and synthesis of myogenic prodromal cells and regulate vascular generation for the continued survival of myocytes. The purpose of the present study was to confirm the effects of electroacupuncture (EA) and electrical stimulation (ES) on muscle recovery processes according to vascular endothelial growth factor (VEGF) expression. Eighteen Sprague-Dawley rats were separated into 2 experimental groups and a controlled group. All animals had suffered from crush damage in the extensor digitorum longus for 30 seconds and were killed 1, 3, and 7 days after injury. 30 Hz and 1 mA impulsion for 15 minutes was applied to the EA experimental groups Zusanli (ST36) and Taichong (LR3) using electroacupuncture and the same stimulation was applied to the ES group using an electrical node. Hematoxyline-Eosin staining and VEGF immunohistochemistry were used to ascertain the resulting muscle recovery. There were few morphological differences between the EA and ES groups, and both groups were observed to have tendencies to decrease atrophy as time passed. In the controlled group, gradually diminishing atrophy could be observed, but their forms were mostly disheveled. There were few differences in VEGF expression between the EA and ES groups, and tendencies to have an increased quantity of VEGF with the lapse of time were observed in both groups. In the controlled group, a little VEGF expression could be observed merely 7 days after injury. In conclusion, EA and ES contributed to muscle recovery processes and could be used for the treatment of muscle injury.

• The Journal of Korean Academy of Prosthodontics
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• v.54 no.3
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• pp.203-209
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• 2016

Purpose: Stimulating the proliferation and migration of periodontal ligament cells (PDLCs) has become the main goal of periodontal regeneration. To accomplish this goal, regeneration procedures have been developed, but results have not been predictable. Recently, tissue engineering using enamel matrix derivatives (EMDs) and growth factors has been applied to periodontal regeneration; however, the mechanism of EMDs is largely unknown. The aim of this study was to investigate the effects of EMDs on the proliferation and release of growth factors from PDLCs. Materials and methods: Human PDLCs were removed from individually extracted 3rd molars of healthy young adults, and cultured in the media containing EMDs (Emdogain, Biora, Malmo, Sweden) at concentration of 0, 12.5, 25, 50, 100, and $200{\mu}g/mL$ each. Cell proliferation and ALP (alkaline phosphatase) activity were measured. The evaluation of growth factors released by PDLCs was also performed by one-way analysis of variance (ANOVA) and Bonferroni's multiple comparison test. Results: Significantly increased proliferation and ALP activity were observed in PDLCs treated with over $25{\mu}g/mL$ and $50{\mu}g/mL$ EMDs, respectively. Additionally, treatment of PDLCs with $50{\mu}g/mL$ resulted in significantly increased release of vascular endothelial growth factor (VEGF) and transforming growth factor $(TGF)-{\beta}$ after 24 h and 48 h, respectively. Conclusion: EMDs enhance the proliferation and ALP activity of PDLCs, and promote the release of growth factors, including VEGF and $TGF-{\beta}$, from PDLCs. Therefore EMDs could be one of the effective methods for periodontal regeneration.

• Journal of Life Science
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• v.26 no.10
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• pp.1189-1195
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• 2016

Vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) are potent angiogenic factors that have been used clinically to induce angiogenesis. To enable migration and invasion, cells must proliferate and secrete proteinases, which degrade the surrounding extracellular matrix. The goal of this study was to investigate the cell proliferation; matrix metalloproteinase-2 (MMP-2), MMP-9, and plasmin secretion; and migration and invasion of glioma-derived U-373-MG cells induced by VEGF and HGF treatment. An additional goal was to test the hypothesis that elevated secretion of MMP-2, MMP-9, and plasmin contributed directly or indirectly to the proliferation, migration, and invasion of U-373-MG cells. Cell proliferation, migration, and invasion and MMP-2, MMP-9, and plasmin secretion were significantly increased in the VEGF and HGF-treated U-373-MG cells. To elucidate the role of the increased secretion of MMP-2, MMP-9, and plasmin in cell proliferation, migration, and invasion of the U-373-MG cells, they were treated with MMPs inhibitor (BB-94) and plasmin inhibitor (α2AP) prior to VEGF or HGF stimulation. The BB-94 and α2AP treatment resulted in a significant reduction in the cell proliferation, migration, and invasion of the U-373-MG cells as compared with the VEGF- and HGF-treated groups. The results indicate that inhibition of MMPs and plasmin reduce the cell proliferation, migration, and invasion of U-373-MG cells.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.36 no.3
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• pp.85-93
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• 2014

Purpose: Nodal metastasis is the main prognostic factor in the patients with oral squamous cell carcinoma (OSCC). We investigated the association between tumor-associated lymphatics and OSCC characteristics. Methods: Thirty-four specimens were used for the immunohistochemical staining with the antibody for vascular endothelial growth factor (VEGF)-C, VEGF-D, VEGF receptor (VEGFR)-3, phosphorylated VEGFR-3, D2-40, and matrix metallproteinases (MMPs). We observed the distribution of the lymphangiogenic factors and quantified the degree of expression. We determined lymphatic vessel density (LVD) and lymphatic vessel dilatation with D2-40 immunostaining. We assessed the association of LVD or lymphatic vessel dilatation with tumor progression or tumor differentiation. Results: OSCC cells expressed lymphangiogenic ligands. Lymphangiogenic receptor, VEGFR-3, was expressed and activated in some tumor cells as well as in tumor-associated endothelial cells. LVD was not associated with tumor size or nodal status, but lymphatic vessel dilatation was higher in tumors with nodal metastasis, and also higher in poorly differentiated tumors. In stromal area of OSCC, MMP-1 and MMP-10 were up-regulated and the basement membrane of tumor-associated endothelial cells was destroyed by these collagenases. Conclusion: In the primary tumors with nodal metastasis, especially in poorly differentiated OSCC, tumor cells invaded the dilated lymphatic vessels via ruptured sites. MMP-1 and MMP-10 are important in the lysis of the glycocalyx inside the tumor-associated lymphatic endothelial cells.

• Genomics & Informatics
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• v.2 no.1
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• pp.36-44
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• 2004

Astrocytes play supportive roles for neurons in the brain. Recently, they have been accepted to have various functions in the vascular system as well as in the nervous system. We investigated the differential gene expression in rat astrocytes according to the oxygen tension, which is a crucial factor for angiogenesis. A cDNA microarray was performed to find the genes whose expression was sensitive to oxygen tension. We found 26 genes in the astrocyte were found and classified into 4 groups. In order to show the genes' relevancy to angiogenesis, seven of the 26 genes were investigated to see whether they have capabilities of interaction with angiogenesis­related factors in AngioDB. Through this investigation, we found interactions of three proteins with angiogenesis-related factors. These genes were further investigated with a new focus on the vascular endothelial growth factor (VEGF) expression in an astrocyte based on our hypothesis that astrocytes can have effects on endothelial angiogenesis via the release of VEGF. Collectively, we identified several genes whose expressions were dependent on the oxygen concentration of the astrocyte. Furthermore, the relevancy of astrocytes to angiogenesis was investigated using preexisting information of AngioDB, and suggested a possible signaling pathway for VEGF expression in the aspects of brain endothelial angiogenesis by astrocytes.

• Applied Microscopy
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• v.43 no.1
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• pp.27-33
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• 2013

Inflammatory cells express the inflammatory cytokines and growth factors induced by lipopolysaccharide (LPS). Odontoblasts are located at the pulp-dentin interface and extend their cell processes far into the dentin where they are the first cells to encounter microorganisms or their products. Therefore, this study examined the expression of some growth factors related to the signal pathway, such as growth factor receptor binding protein 2 (Grb2)-Ras in odontoblast-like dental pulp cells, after a treatment with LPS. After 60 minutes, the mRNA and protein expression levels of Grb2 and Ras were higher in the LPS-treated cells than in the control cells. The level of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) mRNA expression was increased significantly to a level similar to that of Grb2 and Ras at 60 minutes. The platelet-derived growth factor-AA (PDGF-AA) mRNA level was expressed strongly in the odontoblast like dental pulp cells without an association with LPS stimulation. Scanning electron microscopy revealed many extensions of the cytoplasmic processes and the number of processes increased gradually at 30, 60 and 90 minutes after LPS stimulation. From these results VEGF and bFGF expression might be induced through the Grb2-Ras signal transduction pathway in LPS treated odontoblasts.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.21
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• pp.9523-9527
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• 2014

The incidence of colorectal cancer (CRC) is increasing in many Asian countries and microRNAs have already been proven to be associated with tumorigenesis. Currently, microRNA-376a (miR-376a) expression and association with clinical factors in CRC remains unclear. In this study, real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was carried out on 53 matched pairs of CRC and adjacent normal mucosa to investigate the expression levels of miR-376a. According to the high or low expression of miR-376a, patients were divided into two groups. The relationship between miR-376a expression and clinicopathological factors of 53 patients was evaluated. Survival analysis of 53 CRC patients was performed with clinical follow-up information and survival curves were assessed by the Kaplan-Meier method. Immunohistochemistry (IHC) staining was performed on sections of paraffin-embedded tissue to investigate the vascular endothelial growth factor (VEGF) expression. MiR-376a showed low expression in cancer tissues compared to the adjacent normal tissues and altered high miR-376a expression tended to be positively correlated with advanced lymph node metastasis and shorter patient survival. VEGF IHC positivity was significantly more common in patients with high expression levels of miR-376a.Those results demonstrated that miR-376a may be a meaningful prognostic biomarker and potential therapeutic target in colorectal cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2823-2828
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• 2012

Objective: To explore a new model of in-situ xenograft lymphangiogenesis of human colonic adenocarcinomas in nude mice. Method: On the basis of establishing subcutaneous xenograft lymphangiogenesis model of human colonic adenocarcinoms, in-situ xenografts were established through the in situ growth of the HT-29 human colonic adenocarcinoma cell line in nude mice. The numbers of lymphangiogenic microvessels, the expression of lymphatic endothelial cell markers lymphatic vessel endothelial hyaloronic acid receptor-1 (LYVE-1), D2-40 and the lymphatic endothelial growth factors vascular endothelial growth factor-C (VEGF-C), -D (VEGF-D) and receptor-3 (VEGFR-3) were compared by immunohistochemical staining, Western bolt and quantitative RT-PCR in xenograft in-situ models. Results: Some microlymphatics with thin walls, large and irregular or collapsed cavities and increased LMVD, with strong positive of LYVE-1, D2-40 in immunohistochemistry, were observed, identical with the morphological characteristics of lymphatic vessels and capillaries. Expression of LYVE-1 and D2-40 proteins and mRNAs were significantly higher in xenograpfts in-situ than in the negative control group(both P<0.01). Moreover, the expression of VEGF-C, VEGF-D and VEGFR-3 proteins and mRNAs were significantly higher in xenografts in-situ (both P<0.01), in conformity with the signal regulation of the VEGF-C,-D/VEGFR-3 axis of tumor lymphangiogenesis. Conclusions: In-situ xenografts of a human colonic adenocarcinoma cell line demonstrate tumor lymphangiogenesis. This novel in-situ animal model should be useful for further studying mechanisms of lymph node metastasis, drug intervention and anti-metastasis therapy in colorectal cancer.

• 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.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3089-3097
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• 2012

Background and Aims: Vascular endothelial growth factor (VEGF) is a potential prognostic biomarker for patients with resected gastric cancer. However, its role remains controversial. The objective of this study was to conduct a systematic review and meta-analysis of published literature. Methods: Relevant literature was identified using Medline and survival data from published studies were collected following a methodological assessment. Quality assessment of eligible studies and meta-analysis of hazard ratio (HR) were performed to review the correlation of VEGF overexpression with survival and recurrence in patients with gastric cancer. Results: Our meta-analysis included 44 published studies with 4,794 resected patients. VEGF subtype for the prediction of overall survival (OS) included tissue VEGF (HR=2.13, 95% CI 1.71-2.65), circulating VEGF (HR=4.22, 95% CI 2.47-7.18), tissue VEGF-C (HR=2.21, 95% CI 1.58-3.09), tissue VEGF-D (HR=1.73, 95% CI 1.25-2.40). Subgroup analysis showed that HRs of tissue VEGF for OS were, 1.78 (95% CI 0.90-3.51) and 2.31 (95% CI 1.82-2.93) in non-Asians and Asians, respectively. The meta-analysis was also conducted for disease free survival (DFS) and disease specific survival (DSS). Conclusion: Positive expression of tissue VEGF, circulating VEGF, VEGF-C and VEGF-D were all associated with poor prognosis in resected gastric cancer. However, VEGF demonstrated no significant prognostic value for non-Asian populations. Circulating VEGF may be better than tissue VEGF in predicting prognosis.