• Maxillofacial Plastic and Reconstructive Surgery
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• v.30 no.3
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• pp.217-224
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• 2008

Angiogenesis plays an important role in bone development and postnatal bone fracture repair. Vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptors (VEGFRs) have been thought to be primarily involved in promoting angiogenesis. It is well known that VEGF and its receptors have been reported to play an important role in the regulation of the interaction between angiogenesis and osteogenesis during bone repair processes. Dexamethasone, a potent synthetic glucocorticoid, promotes phenotype markers of osteoblast differentiation, such as ALP and osteocalcin. It stimulates in vitro osteogenesis of human bone marrow osteogenic stromal cells. Dexamethasone has been reported to suppress VEGF gene expression in some cells. However, our previous study demonstrated VEGF quantification increased in a time-dependent manner in periosteal-derived osteogenesis under dexamethasone. So, the purpose of this study was to examine the angiogenic phenotypes in cultured human periosteal-derived cells under high-dose dexamethasone. Periosteal-derived cells were cultured using a technique previously described. After passage 3, the periosteal-derived cells were further cultured for 28 days in an osteogenic inductive culture medium containing ascorbic acid, ${\beta}$-glycerophosphate and high-dose dexamethasone, We evaluated the expression of VEGF isoforms, VEGFR-1, VEGFR-2, and neuropilin-1, ALL VEGF isoforms ($VEGF_{121},\;VEGF_{165},\;VEGF_{189}$, and $VEGF_{206}$) expression was observed by RT-PCR analysis. VEGFR-1, VEGFR-2 and neuropilin-1 expression increased up to day 14, particularly during the early stage of mineralization. Our results suggest the involvement of direct VEGFs/VEGFRs system on periosteal-derived cells during early mineralization phase under high-dose of dexamethasone. These also suggest that VEGF might act as an autocrine growth molecule during osteoblastic differentiation of cultured human periosteal-derived cells.

• Journal of Life Science
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• v.27 no.1
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• pp.78-88
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• 2017

Angiogenesis, the formation of new blood vessels, plays an important role in tumor growth and metastasis; therefore, it has become an important target in cancer therapy. Novel anticancer pharmaceutical products that have relatively few side effects or are non-cytotoxic must be developed, and such products may be obtained from traditional herbal medicines. Coptis chinensis Franch. is an herb used in traditional medicine for the treatment of inflammatory diseases and diabetes. However, potential antiangiogenic effects of C. chinensis water extract (CCFWE) have not yet been studied. The purpose of this study was to determine the antiangiogenic effect of CCFWE in order to evaluate its potential for an anticancer drug. We found that the treatment with CCFWE inhibited the major steps of the angiogenesis process, such as the endothelial cell proliferation, migration, invasion, and capillary-like tube formation in response to vascular endothelial growth factor (VEGF), and also resulted in the growth inhibition of new blood vessels in an ex vivo rat aortic ring assay. We also observed that CCFWE treatment arrested the cell cycle at the G0/G1 phase, preventing the G0/G1 to S phase cell cycle progression in response to VEGF. In addition, the treatment reduced the VEGF-induced activation of matrix metalloproteinases 2 and 9. Taken together, these findings indicate that CCFWE should be considered a potential anticancer therapy against pathological conditions where angiogenesis is stimulated during tumor development.

• Journal of Physiology & Pathology in Korean Medicine
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• v.36 no.5
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• pp.175-180
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• 2022

The seeds of Trichosanthes kirilowii (STK) used in traditional Oriental medicine for the treatment of dry cough and constipation have diverse pharmacological activities, including hypolipidemic, antioxidant, immunosuppressive, and anticancer effects. However, the effect of STK on angiogenesis has not been studied yet. In this study, we investigated whether the ethanolic extract of STK (ESTK) can regulate the migration and tube formation of human umbilical vein endothelial cells (HUVECs) and explored the underlying mechanism. Results of transwell assay showed that ESTK treatment dose-dependently suppressed the migration of HUVECs. The conditioned medium collected from H1299 human lung cancer cells was used as a chemoattractant. Our observation suggests that ESTK would inhibit the recruitment of endothelial cells into tumors. In addition, ESTK treatment significantly reduced the tube formation of HUVECs. As a molecular mechanism, we found that vascular endothelial growth factor (VEGF)-induced phosphorylation of VEGF receptor 2 (VEGFR2) was completely blocked by ESTK treatment. The expression of angiogenic factors, including VEGFA, fibroblast growth factor 2 (FGF2), angiopoietin, placental growth factor (PGF), platelet derived growth factor (PDGF), angiogenin, and tumor necrosis factor (TNF)-α, was commonly decreased by ESTK treatment in H1299 cells, indicating that ESTK would reduce the production of angiogenic factors from cancer cells. Taken together, our results clearly demonstrated that ESTK exhibited anti-angiogenic effects in HUVECs, which provides another possible mechanism underlying the anticancer activities of STK.

• Clinical and Experimental Pediatrics
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• v.49 no.2
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• pp.192-197
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• 2006

Purpose : Vascular endothelial growth factor(VEGF) is a key cytokine for controlling vascular permeability and angiogenesis, which is one of the major findings in airway remodeling. However, it is not well known if it is associated with acute lower respiratory tract disease such as lobar pneumonia. The aim of this study is to compare serum VEGF levels in patients with asthma according to its severity and duration of cough, and to compare its levels with children with lobar pneumonia. Methods : Using a sandwich enzyme-linked immunosorbent assay, the serum VEGF levels were measured in 16 mild asthmatics, 14 moderate to severe asthmatics, six children with lobar pneumonia, and 22 control subjects. The asthmatics were also classified into three groups according to the duration of cough. Serum VEGF levels were compared in each group. Results : Serum VEGF levels were significantly increased in the children with moderate to severe asthma and lobar pneumonia compared to the children with mild asthma and control subjects. Serum VEGF levels were higher in children with chronic coughs of more than two weeks than in children with coughs lasting less than two weeks. Serum levels of VEGF showed positive correlations with blood platelet and white blood cell counts. Conclusion : VEGF increased according to the severity of asthma and duration of cough in children with asthma. It may play an important role not only in chronic airway inflammation, but also in the acute inflammation in children with lower respiratory tract disease.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.1
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• pp.97-101
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• 2015

Background: The gene for the vascular endothelial growth factor (VEGF), which promotes angiogenesis and permeability, is polymorphic. The aim of the present study was to evaluate the relationship between +936C>T and +404C>G polymorphism of VEGF with risk of esophageal cancer in the Kashmiri population in India. Materials and Methods: 150 esophageal cancer patients and 150 unrelated healthy controls were genotyped for two VGEF SNPs (+405C/G, and +936C/T) using DNA extracted from prospectively collected blood samples by the PCR-RFLP method. Results: For the VEGF +936C>T polymorphism a significant association of CT and combined CT+TT genotypes was observed with increased risk of esophageal cancer (p=0.021; 0.024). For the +405C>G polymorphism we observed significantly increased frequency of GG genotype in cases as compared to controls and also the +405 GG Genotype was observed to have a two fold risk(OR=2.7356; 95%CI=1.1409-6.5593; p=0.020). The combined genotypes of GG-CC and GG-CT of +405C>G and +936C>T were found to be significantly associated with increased risk of esophageal cancer (p=0.0376; 0.0099). Conclusions: From the results of the present study a significant association of +936C>T and +405C>G polymorphisms with increased esophageal cancer risk exists in the Kashmiri population.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.12
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• pp.5303-5307
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• 2016

Objective: Brain tumors cause great mortality and morbidity worldwide, and success rates with surgical treatment remain very low. Several recent studies have focused on introduction of novel effective medical therapeutic approaches. Genistein is a member of the isoflavonoid family which has proved to exert anticancer effects. Here we assessed the effects of genistein on the expression of MMP-2 and VEGF in low and high grade gliomas in vitro. Materials and Methods: High and low grade glioma tumor tissue samples were obtained from a total of 16 patients, washed with PBS, cut into small pieces, digested with collagenase type I and cultured in DMEM containing 10% FBS. When cells reached passage 3, they were exposed to genistein and MMP-2 and VEGF gene transcripts were determined by quantitative real time PCR (qRT-PCR). Results: Expression of MMP-2 demonstrated 580-fold reduction in expression in low grade glioma cells post treatment with genistein compared to untreated cells (P value= 0.05). In cells derived from high grade lesions, expression of MMP-2 was 2-fold lower than in controls (P value> 0.05). Genistein caused a 4.7-fold reduction in VEGF transcript in high grade glioma cells (P value> 0.05) but no effects were evident in low grade glioma cells. Conclusion. Based on the data of the present study, low grade glioma cells appear much more sensitive to genistein and this isoflavone might offer an appropriate therapeutic intervention in these patients. Further investigation of this possibility is clearly warranted.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.35 no.1
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• pp.1-12
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• 2013

Purpose: Vascular endothelial growth factor (VEGF)-C and its tyrosine kinase receptor, VEGF receptor (VEGFR)-3 are recently known to have lymphangiogenic activities in various tumor types. In this study, we determined whether the expression of lymphangiogenic factors correlate with nodal metastasis or survival in a nude mouse model of oral squamous cell carcinoma (OSCC). Methods: Three OSCC cells (KB, SCC4, SCC9) were xenografted into the right mandibular gland of athymic nude mice. The mice were followed for tumor development and growth, and the mice were sacrificed when they had lost more than 20% of their initial body weight, or the diameter of the induced tumor exceeds 20 mm. After necropsy, the murine tumors were examined histologically and radiologically (micro-positron emission tomography computed tomography) for regional or distant metastasis. We performed immunohistochemical assays with anti-VEGF-C, VEGFR-3, CD105, and D2-40 antibodies. Immunofluorescence double staining for LYVE-1/CD31 was also performed. To quantify the VEGF-C and VEGFR-3 level in the cancer tissue, Western blotting was performed. Finally, we determined the correlation between the degree of expression of VEGF-C/VEGFR-3 and the mean survival time. Results: OSCC tumor cells into the mandibular gland of the nude mice successfully resulted in the formation of recapitulating orthotopic tumor. Tumor cells of the induced tumor did not express VEGF-C. VEGF-C/VEGFR-3 expression was mainly distributed in the endothelial cells of the stromal area. There were no correlation between the degree of expression of VEGF-C/VEGFR-3 and the mean survival time of mice injected with different OSCC cell lines. Conclusion: An recapitulating orthotopic model of OSCC in nude mice was established, which copies the cervical nodal metastasis of human OSCC. Overexpression of lymphangiogenic factors seems to have no effect on survival of hosts in this in vivo experiment.

• Korean Journal of Head & Neck Oncology
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• v.18 no.1
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• pp.23-29
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• 2002

Mutation of the P53 tumor suppressor gene playa major role in the development of many carcinomas, namely in the colon, breast and bladder, whereas the role played by such mutations in thyroid carcinogenesis remains controversial. Vascular endothelial growth factor (VEGF) induces proliferation of endothelial cells, stimulates angiogenesis, and increases vascular permeability. Increased VEGF expression has been associated with poor clinical outcomes in many malignancies E-cadherin, a calcium-dependent transmembrane glycoprotein, is an adhesion molecule Expression of p53, VEGF and E-cadherin was assessed immunohistochemically in 19 tall columnar variant of papillary carcinoma, 24 common papillary carcinoma and 7 follicular carcinoma. The aim of this study was to evaluate the expression of P53,VEGF and E-cadherin as a potential maker for the prognosis of thyroid carcinomas. The results are as follows: 1) There were no significance in any clinical parameters examined among tall columnar variant of papillary carcinoma, common papillary carcinoma and follicular carcinoma. 2) The expression of P53 demonstrated low in tall columnar variant of papillary carcinoma, common papillary carcinoma and follicular carcinoma, but a significantly high in regional lymph node metastasis. 3) The expression of VEGF demonstrated a significantly high in regional lymph node metastasis than those without metastasis in papillary thyroid carcinoma. 4) The expression of E-cadherin demonstrated less often among papillary carcinomas with lymph node metastasis than in those without metastasis in papillary thyroid carcinoma. In conclusion, it is suggested that VEGF and E-cadherin will be useful for the diagnosis of thyroid carcinoma and serves as a biological marker for thyroid carcinoma lymph node metastasis.

• Biomolecules & Therapeutics
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• v.27 no.1
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• pp.117-125
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• 2019

Mebendazole (MBZ), a microtubule depolymerizing drug commonly used for the treatment of helminthic infections, has recently been noted as a repositioning candidate for angiogenesis inhibition and cancer therapy. However, the definite anti-angiogenic mechanism of MBZ remains unclear. In this study, we explored the inhibitory mechanism of MBZ in endothelial cells (ECs) and developed a novel strategy to improve its anti-angiogenic therapy. Treatment of ECs with MBZ led to inhibition of EC proliferation in a dose-dependent manner in several culture conditions in the presence of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) or FBS, without selectivity of growth factors, although MBZ is known to inhibit VEGF receptor 2 kinase. Furthermore, MBZ inhibited EC migration and tube formation induced by either VEGF or bFGF. However, unexpectedly, treatment of MBZ did not affect FAK and ERK1/2 phosphorylation induced by these factors. Treatment with MBZ induced shrinking of ECs and caused G2-M arrest and apoptosis with an increased Sub-G1 fraction. In addition, increased levels of nuclear fragmentation, p53 expression, and active form of caspase 3 were observed. The marked induction of autophagy by MBZ was also noted. Interestingly, inhibition of autophagy through knocking down of Beclin1 or ATG5/7, or treatment with autophagy inhibitors such as 3-methyladenine and chloroquine resulted in marked enhancement of anti-proliferative and pro-apoptotic effects of MBZ in ECs. Consequently, we suggest that MBZ induces autophagy in ECs and that protective autophagy can be a novel target for enhancing the anti-angiogenic efficacy of MBZ in cancer treatment.

• Tuberculosis and Respiratory Diseases
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• v.52 no.2
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• pp.137-144
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• 2002

Background: Hemoptysis is an often alarming presenting symptom and VEGF is a major regulator of both normal and abnormal angiogenesis, including many inflarrunatory diseases. In this report the clinical significance of the serum VEGF level in patients with hemoptysis was investigated. Methods: Thirty-two patients with hemoptysis were evaluated. The estimated amount of hemoptysis, etiology and serum VEGF level was examined at admission and bronchial angiography was performed in 22 patients. In order to objectify the neovascularization status, one point for the presence of the A-V shunt, hypervascularity, vascular tortuosity was designated for a total of 0-3 points. Results: Mean quantity of hemoptysis was $172.4{\pm}270.4ml$. The mean angiographic neovascularization score was $1.23{\pm}0.75$. The serum VEGF level correlated with the quantity of hemoptysis(r=0.524, p=0.002) and with the angiographic neovascularization score(r=0.441, p=0.04). Using the standard diagnostic criterion for massive hemoptysis, the serum VEGF level of patients with massive hemoptysis($642.4{\pm}545.6$ pg/ml, n=13) was found to be higher than that of patients with non-massive hemoptysis($394.6{\pm}225.8$ pg/ml, n=19) (p=0.069). Conclusion: Regardless of the etiology, the serum VEGF may contribute to abnormal neovascularization in patients with hemoptysis. Therefore, it is suggested that serum VEGF measurements may help in predicting a massive hemoptysis.