• Journal of Korean Neurosurgical Society
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• 제51권6호
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• pp.328-333
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• 2012

Objective : The aim of this study is to determine the association between the cerebrospinal fluid (CSF) biomarkers and inflammation, and the predictive value of these CSF biomarkers for subsequent shunt associated infection. Methods : We obtained CSF samples from the patients with hydrocephalus during ventriculoperitoneal (VP) shunt operations. Twenty-two patients were enrolled for this study and divided into 3 groups: subarachnoid hemorrhage (SAH)-induced hydrocephalus, idiopathic normal pressure hydrocephalus (INPH) and hydrocephalus with a subsequent shunt infection. We analyzed the transforming growth factor-${\beta}1$, tumor necrosis factor-${\alpha}$, vascular endothelial growth factor (VEGF) and total tau in the CSF by performing enzyme-linked immunosorbent assay. The subsequent development of shunt infection was confirmed by the clinical presentations, the CSF parameters and CSF culture from the shunt devices. Results : The mean VEGF concentration (${\pm}$standard deviation) in the CSF of the SAH-induced hydrocephalus, INPH and shunt infection groups was $236{\pm}138$, $237{\pm}80$ and $627{\pm}391$ pg/mL, respectively. There was a significant difference among the three groups (p=0.01). Between the SAH-induced hydrocephalus and infection groups and between the INPH and infection groups, there was a significant difference of the VEGF levels (p<0.01). However, the other marker levels did not differ among them. Conclusion : The present study showed that only the CSF VEGF levels are associated with the subsequent development of shunt infection. Our results suggest that increased CSF VEGF could provide a good condition for bacteria that are introduced at the time of surgery to grow in the brain, rather than reflecting a sequel of bacterial infection before VP shunt.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제36권3호
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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.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제35권2호
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• pp.55-65
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• 2009

Purpose: We determined the therapeutic effects of blockade of epidermal growth factor(EGF) and vascular endothelial growth factor(VEGF) receptor tyrosine kinases on the growth of oral squamous cell carcinoma(OSCC) xenografted in athymic nude mice. Experimental Design: We investigated the in vivo antitumor effects of a tyrosine kinase inhibitor for EGFR and VEGFR-2, AEE788 in a mouth floor(orthotopic) tumor model. Nude mice with orthotopic tumors were randomized to receive AEE788, paclitaxel, a combination of AEE788 and paclitaxel, or control. Antitumor mechanisms of AEE788 were determined by immunohistochemical/immunofluorescent and apoptosis assays. Results: Tumors of mice treated with AEE788 demonstrated down-regulation of phosphorylated EGFR, phosphorylated VEGFR and their downstream mediators(pMAPK and pAkt), decreased proliferative index, decreased microvessel density(MVD). As a result, growth of the primary tumor and nodal metastatic potentials were inhibited by AEE788. Conclusion: These data show that EGFR and VEGFR can be molecular targets for the treatment of OSCC.

• Archives of Pharmacal Research
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• 제28권11호
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• pp.1270-1274
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• 2005

The vascular endothelial growth factor (VEGF) plays a key role in angiogenesis, which is a process where new blood vessels develop from the endothelium of a pre-existing vasculature. VEGF exerts its activity by binding to its receptor tyrosine kinase, KDR/Flk-1, which is expressed on the surface of endothelial cells. A methanol extract and organic solvent (n-hexane, ethyl acetate, n-butanol, aqueous) fractions from Rubus coreanus were examined for their inhibitory effects on VEGF binding to the VEGF receptor. The methanol extract from the crude drug were found to significantly inhibit VEGF binding to the VEGF receptor ($IC_{50}$$\thickapprox$27 $\mu$g/mL). Among the fractions examined, the aqueous fraction from the medicinal plant showed potent inhibitory effects against the binding of KDR/Flk-1-Fc to immobilized $VEGF_{165}$ in a dose­dependent manner ($IC_{50}$$\thickapprox$11 $\mu$g/mL). Sanguiin H-6 was isolated as an active principle from the aqueous fraction, and inhibited the binding of KDR/Flk-1-Fc to immobilized $VEGF_{165}$ in a dose­dependent manner ($IC_{50}$$\thickapprox$0.3 $\mu$g/mL). In addition, sanguiin H-6 efficiently blocked the VEGF­induced HUVEC proliferation in a dose-dependent manner ($IC_{50}$$\thickapprox$7.4 $\mu$g/mL) but had no effect on the growth of HT1080 human fibrosarcoma cells. This suggests that sanguiin H-6 might be a potential anti-angiogenic agent.

• Toxicological Research
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• 제24권3호
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• pp.169-174
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• 2008

This study examined the mechanisms underlying the effects of the vasorelaxation active substance(VAS), dimethyladenosine-5'-L-arabinose, and its partial purification fraction on nitric oxide synthase in improving erectile dysfunction with particular focus on the nitric oxide (NO)-cGMP pathways. Two rat models, 9-month-old SD rats and 11-month-old SD rats, were given VAS(40 mg/kg per day) for 4 days, The aqueous fraction of silworm male pupae extract; semi-purified VAS(100 mg/kg per day) for 10 days, respectively. The NOS activities of the following three enzymes were examined: neuronal NO synthase(nNOS), inducible NOS(iNOS), endothelial NOS(eNOS), vascular endothelial growth factor on endothelial cells(VEGF) and anti-inflammation effect of Tumor necrosis factor-$\alpha$. The results showed increases in the nitric oxide synthase activities. Western blotting of the tissue homogenate showed an increase in the nNOS level in the brain and tongue, and an increase in the endothelial NO synthase(eNOS) level in penis. However, there was little association with VEGF production in HUVEC endothelial cells and no relationship with TNF-$\alpha$ which showed low levels.

• Clinical and Experimental Pediatrics
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• 제51권5호
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• pp.487-491
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• 2008

목 적 : 마이코플라스마 폐렴은 일부 천식의 과거력이 없는 환자에서도 천명, 호흡곤란 등의 증상을 보여 천식의 발생과 관계된다고 한다. VEGF는 천식의 만성 염증 형성에 중요한 역할을 한다. 본 연구는 마이코플라스마 폐렴에서 천명이 동반되는 환아와 천명이 없는 환아에서 혈청 VEGF의 농도가 차이가 있는지 알아보고자 하였다. 방 법 : 2006년 8월부터 2007년 2월까지 고려대학교 안암병원 소아과에 천식의 과거력이 없는 마이코플라스마 폐렴으로 입원한 환아들 중 의사의 청진상 천명음이 처음으로 확인된 환아 9명(천명군)과 천명음이 한번도 없었던 비천명군 63명을 대상으로 혈청 VEGF농도, M. pneumoniae 항체가, 혈액 호산구 염증지표 및 혈청 IgE 농도 등을 측정하였다. 결 과 : 천명군의 혈청 VEGF 농도는 $650.2{\pm}417.9pg/mL$로 비천명군($376.5{\pm}356.2pg/mL$) 보다 높게 나타났고(P=0.049), M. pneumoniae 항체가도 천명군에서 더 높았다(1:1,380 vs. 1:596, P=0.048). 혈청 총IgE 값은 천명군이 591.8 IU/mL, 비천명군이 162.2 IU/mL 이었다(P=0.032). 두 군의 말초혈액 호산구수(천명군 : $263.0/{\mu}L$ vs. 비천명군 : $166.5/{\mu}L$)와 혈청 ECP 농도(천명군 : $22.8{\mu}g/L$ vs. 비천명군 : $17.4{\mu}g/L$)는 유의한 차이가 없었다. 천명군에서 혈청 VEGF 농도는 항체가와 유의한 상관관계를 보였다(r=0.568, P=0.034). 결 론 : 천식의 과거력이 없는 아토피 소아에서 높은 VEGF 농도는 마이코플라스마 폐렴에서 천명 발생과 관계가 있는 것으로 생각할 수 있으며, 이들 환자에서 앞으로 천식 발생 유무에 대한 추적 관찰이 필요하리라 생각한다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권22호
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• pp.9713-9717
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• 2014

Background: Colon cancer (CRC) is perhaps the second most common cause of cancer mortality. This study determined the clinical significance of serum vascular endothelial growth factor (VEGF) and serum complement 3a (C3a) levels in patients with CRC in Fars province, southern Iran. Materials and Methods: Between June 2010 and June 2012, 110 patients with CRC of both genders and different age groups were divided into 3 groups. Group A included patients who had just undergone surgery; Group B had undergone chemotherapy after surgery; and Group C had undergone chemotherapy and radiotherapy after surgery. Twenty one healthy subjects with normal colonoscopy were considered as a control group. ELISA was undertaken to determine VEGF and C3a levels before and after treatment measures. Results: The mean age of patients was $53.9{\pm}14.1$ years. Considering VEGF level, a significant decrease was visible after treatment measures in groups A and B, but not Group C. For VEGF level, the difference was not statistically significant between two genders and various age groups before and after treatment. No significant difference was found for VEGF level between patients and normal group before any treatment. Regarding C3a levels in 101 subjects, they significantly decreased after treatment measures. Before and after treatment, the difference was statistically significant between two genders, but was not statistically significant among various age groups. Conclusions: As VEGF and C3a levels were significantly lower in patients after treatment, these may be beneficial markers in assessment of CRC therapy especially in early stages.

• Nutrition Research and Practice
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• 제15권4호
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• pp.444-455
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• 2021

BACKGROUND/OBJECTIVES: Adipocytes undergo angiogenesis to receive nutrients and oxygen needed for adipocyte' growth and differentiation. No study relating quercetin with angiogenesis in adipocytes exists. Therefore, this study investigated the role of quercetin on adipogenesis in 3T3-L1 cells, acting through matrix metalloproteinases (MMPs). MATERIALS/METHODS: After proliferating preadipocytes into adipocytes, various quercetin concentrations were added to adipocytes, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were performed to evaluate cell proliferation. Glycerol-3-phosphate dehydrogenase (GPDH) activity was investigated as an indicator of fat accumulation. The mRNA expressions of transcription factors related to adipocyte differentiation, CCAAT/enhancer-binding proteins (C/EBPs), peroxisomal proliferatoractivated receptors (PPAR)-γ, and adipocyte protein 2 (aP2), were investigated. The mRNA expressions of proteins related to angiogenesis, vascular endothelial growth factor (VEGF)-α, vascular endothelial growth factor receptor (VEGFR)-2, MMP-2, and MMP-9, were investigated. Enzyme activities and concentrations of MMP-2 and MMP-9 were also measured. RESULTS: Quercetin treatment suppressed fat accumulation and the expressions of adipocyte differentiation-related genes (C/EBPα, C/EBPβ, PPAR-γ, and aP2) in a concentration-dependent manner in 3T3-L1 cells. Quercetin treatments reduced the mRNA expressions of VEGF-α, VEGFR-2, MMP-2, and MMP-9 in 3T3-L1 cells. The activities and concentrations of MMP-2 and MMP-9 were also decreased significantly as the concentration of quercetin increased. CONCLUSIONS: The results confirm that quercetin inhibits adipose tissue differentiation and fat accumulation in 3T3-L1 cells, which could occur through inhibition of the angiogenesis process related to MMPs.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제28권3호
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• pp.193-201
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• 2006

Squamous cell carcinoma(SCC) of head and neck(SCCHN) is the sixth most common human malignant tumor. However, despite advances in prevention and treatment of SCC, the five-year survival rates for patients remain still low. To improve the outcome for patients with SCCHN, novel treatment strategies are needed. Overexpression of the epidermal growth factor(EGF) and activation of its receptor(EGFR) are associated with progressive growth of SCCHN. Vascular endothelial growth factor(VEGF) signaling molecules are related with neoangiogenesis and vascular metastasis of SCC. In this study, we determined the therapeutic effect of AEE788(Novartis Pharma AG, Basel, Switzerland), which is a dual inhibitor of EGFR/ErbB2 and VEGFR tyrosine kinases, on human oral SCC. At first, we screened the expression of EGFR, c-ErbB2(HER-2) and VEGFR-2 in a series of human oral SCC cell lines. And then we evaluated the effects of AEE788 on the phosphorylation of EGFR and VEGFR-2 in a oral SCC cell line expressing EGFR/HER-2 and VEGFR-2. We also evaluated the effects of AEE788 alone, or with paclitaxel(Taxol) on the oral SCC cell growth and apoptosis. As a result, all oral SCC cells expressed EGFR and VEGFR-2. Treatment of oral SCC cells with AEE788 led to dose-dependent inhibition of EGFR and VEGFR-2 phosphorylation, growth inhibition, and induction of apoptosis. Moreover, AEE788 sensitizes the cells to paclitaxel-mediated toxicity and apoptosis. These data mean EGFR and VEGFR-2 can be reliable targets for molecular therapy of oral SCC, and therefore warrant clinical use of EGFR/VEGFR inhibition in the treatment of patients with recurrent or metastatic oral SCC.

• Journal of Microbiology and Biotechnology
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• 제18권1호
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• pp.183-187
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• 2008

Vascular endothelial growth factors (VEGFs) are a family of proteins that mediate angiogenesis. $VEGF_{165}$ is a VEGF-A isoform and has been extensively studied owing to its potential use in therapeutic angiogenesis. This study established Chinese hamster ovary (CHO) cells overexpressing recombinant human $VEGF_{165}$ $(rhVEGF_{165})$ protein. The production rate of the established CHO cells was over 80mg/l of $rhVEGF_{165}$ protein from a 7-day batch culture process using a 7.5-l bioreactor with a 5-l working volume and serum-free medium. The $rhVEGF_{165}$ protein was purified to homogeneity from the culture supernatant using a two-step chromatographic procedure that resulted in a 48% recovery rate. The purified $rhVEGF_{165}$ protein was a glycosylated homodimeric protein with a higher molecular weight (MW) than the protein expressed from insect cells, suggesting that the glycosylation of the $rhVEGF_{165}$ protein in CHO cells differed from that in insect cells. The purified $rhVEGF_{165}$ protein in this study was functionally active with a half-maximal effective concentration of 3.8ng/ml and specific activity of $2.5{\times}10^5U/mg$.