• BMB Reports
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• v.52 no.9
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• pp.560-565
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• 2019

Benign prostatic hyperplasia (BPH), a common disease in elderly males, is accompanied by non-malignant growth of prostate tissues, subsequently causing hypoxia and angiogenesis. Although VEGF-related angiogenesis is one of the therapeutic targets of prostate cancer, there is no previous study targeting angiogenesis for treatment of BPH. Dihydrotestosterone (DHT)-induced expressions of vascular endothelial growth factor (VEGF) in prostate epithelial RWPE-1 cells and human umbilical vascular endothelial cells (HUVECs). Conditioned media (CM) from DHT-treated RWPE-1 cells were transferred to HUVECs. Then, 6SL inhibited proliferation, VEGFR-2 activation, and tube formation of HUVECs transferred with CM from DHT-treated RWPE-1 cells. In the rat BPH model, 6SL reduced prostate weight, size, and thickness of the prostate tissue. Formation of vessels in prostatic tissues were also reduced with 6SL treatment. We found that 6SL has an ameliorative effect on in vitro and in vivo the BPH model via inhibition of VEGFR-2 activation and subsequent angiogenesis. These results suggest that 6SL might be a candidate for development of novel BPH drugs.

• Tuberculosis and Respiratory Diseases
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• v.64 no.3
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• pp.200-205
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• 2008

Background: Tumor angiogenesis plays an important role in tumor growth, maintenance and metastatic potential. Tumor tissue produces many types of angiogenic growth factors. Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) have both been implicated to have roles in tumor angiogenesis. In this study, the expression of tissue VEGF and bFGF from non-small cell lung cancer (NSCLC) patients were analyzed. Methods: We retrospectively investigated 35 patients with a histologically confirmed adenocarcinoma or squamous cell carcinoma of the lung, where the primary curative approach was surgery. An ELISA was employed to determine the expression of VEGF and bFGF in extracts prepared from 35 frozen tissue samples taken from the cancer patients. Results: VEGF and bFGF concentrations were significantly increased in lung cancer tissue as compared with control (non-cancerous) tissue. The VEGF concentration was significantly increased in T2 and T3 cancers as compared with T1 cancer. Expression of VEGF was increased in node-positive lung cancer tissue as compared with node-negative lung cancer tissue (p=0.06). VEGF and bFGF expression were not directly related to the stage of lung cancer and patient survival. Conclusion: Expression of VEGF and bFGF were increased in lung cancer tissue, and the expression of VEGF concentration in lung cancer tissue was more likely related with tumor size and the presence of a lymph node metastasis than the expression of bFGF. However, in this study, expression of both VEGF and bFGF in tissue were not associated with patient prognosis.

• Biomedical Science Letters
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• v.20 no.4
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• pp.209-220
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• 2014

Vascular endothelial growth factor (VEGF) is a key factor involved in the induction of angiogenesis and has become an attractive target for anti-angiogenesis therapies. The purpose of this study was to elucidate the anti-angiogenic activity of Rubus coreanus Miquel water extract (RCME). Rubus coreanus Miquel has long been employed as a traditional medicine, and recent studies have demonstrated that it has measureable biological activities. Thus, we investigated for the first time the effect of RCME on angiogenesis and its underlying signaling pathways. The effects of RCME were tested on in vitro models of angiogenesis, namely, proliferation, migration, invasion and tube formation of human umbilical vein endothelial cells as well as an ex vivo model of vessel sprouting from the rat aorta in response to VEGF. We observed that VEGF-induced angiogenesis was strongly suppressed by RCME treatment compared to that of the control group. Moreover, we found that RCME inhibited VEGF-induced activation of matrix metalloproteinases and phosphorylation of extracellular signal-regulated kinase and p38, and also effectively inhibited phosphorylation of VEGF receptor 2. These results indicated that RCME inhibits angiogenesis by suppressing phosphorylation of the VEGF receptor and may be useful for the treatment of angiogenesis-dependent diseases such as cancer and diabetic retinopathy.

• Tuberculosis and Respiratory Diseases
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• v.55 no.5
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• pp.467-477
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• 2003

Background : Pleural effusions are generally divided into transudates and exudates. If it is exudative, more diagnostic tests are required in order to determine the cause of the local disease. A malignancy is a common and important cause of exudative pleural effusions. Because the pleural fluid cytology and pleural biopsy specimens do not provide a diagnosis in a high percentage of malignant effusions, several tumor markers have been examined. In order to overcome this limitation, this study hypothesized that C-reactive protein(CRP) and vascular endothelial growth factor(VEGF) measurements would be useful for differentiating trasudates from exudates and determining the differences between a benign and malignant effusion. Methods : Eighty consecutive patients with a pleural effusion (tuberculous 20, parapneumonic 20, malignant 20, transudative 20) were examined prospectively: 60 of them were classified according to Light's criteria as having an exudative fluid and 20 had a transudative fluid. The standard parameters of a pleural effusion were examined and the serum and pleural effusion VEGF levels were measured using enzyme linked immunosorbent assay(ELISA). CRP in the serum and pleural fluid was determined by a turbidimetric immunoassay. Results : The pleural CRP levels in the exudates were significantly higher than those in the transudates, $4.19{\pm}4.22mg/d{\ell}$ and $1.29{\pm}1.45mg/d{\ell}$, respectively. The VEGF levels in the pleural effusions were significantly elevated in the exudates compared to the transudate, $1,011{\pm}1,055pg/m{\ell}$ and $389{\pm}325pg/m{\ell}$, respectively. The VEGF ratio in the exudative effusion is significantly higher than a transudative effusions, $3.9{\pm}4.7$ and $1.6{\pm}0.9$, respectively. The pleural CRP levels in the patients with a benign effusion($4.15{\pm}4.20mg/d{\ell}$) were significantly higher than those in the malignant effusion($1.43{\pm}1.91mg/d{\ell}$). The VEGF ratio is significantly higher in malignant effusions($4.9{\pm}5.5$) than in benign effusions($2.8{\pm}3.6$). Conclusion : In conclusion, the CRP and VEGF levels in the serum and pleural effusion can distinguish between transudates and exudates. Moreover it can differentiate between benign and malignant pleural effusions.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.34 no.1
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• pp.59-70
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• 2008

Purpose: We evaluated the therapeutic effect of AEE788, a dual inhibitor of epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) receptor tyrosine kinases on human salivary adenoid cystic carcinoma (ACC) cells growing in nude mice. Experimental Design: We examined the effects of AEE788 on salivary ACC cell growth and apoptosis. To determine the in vivo effects of AEE788, nude mice with orthotopic parotid tumors were randomized to receive oral AEE788 (50 mg/kg) three times per week, injected paclitaxel ($200{\mu}g$) once per week, AEE788 plus paclitaxel, or placebo. Mechanisms of in vivo AEE788 activity were determined by immunohistochemical analysis. Results: Treatment of salivary ACC cells with AEE788 led to growth inhibition and induction of apoptosis. AEE788 inhibited tumor growth and prevented lung metastasis in nude mice. Furthermore, AEE788 potentiated growth inhibition and apoptosis of ACC tumor cells mediated by paclitaxel. Tumors of mice treated with AEE788 and AEE788 plus paclitaxel exhibited down-regulation of activated EGFR and its downstream mediators (Akt and MAPK), increased tumor and endothelial cell apoptosis, and decreased microvessel den-sity, which correlated with a decrease in the level of MMP-9, MMP-2 and bFGF expression and a decrease in the incidence of vascular metastasis. Conclusions: These data show that tumor-associated endothelial cells are important in the process of tumor-metastasis. And VEGFR can be a molecular target for therapy of metastatic lung lesion of salivary ACC.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.3
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• pp.2053-2058
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• 2013

Background: Formation of new blood vessels is necessary for the development and spread of neoplasms more than 1 mm3 in volume, angiogenesis being responsible for formation of new from pre-existing blood vessels. Vascular endothelial growth factor (VEGF) is pivotal and the best studied angiogenic factor in all human cancers. Therefore we designed this study to investigate the role of VEGF-A and VEGF-C in prostate cancer in comparison with BPH controls in a north Indian population. Methods: In this case-control study a total of 100 subjects were included on the basis of confirmed histopathological reports, out of which 50 were prostate cancer patients and the other 50 were BPH patients with PSA levels >2 ng/ml and abnormal digital rectal examination (DRE) findings during September 2009 to August 2011 from the Department of Urology, KGMU, Lucknow, India. Plasma levels of VEGF were determined using quantitative immunoassay (ELISA-enzyme linked immunosorbent assay). Statistical analysis was carried out using SPSS 15.0 version. Results: The mean age of prostate cancer ($67.6{\pm}5.72$) patients was significantly higher (p=0.005) than BPH ($63.6{\pm}7.92$) patients. Expression of VEGF-A was not significantly higher in disease stage C1 than D1 or D2 and A or B (p=0.13) while the level of VEGF-A was significantly higher (p=0.04) in prostate cancer as compared to BPH subjects (PCa=13.0 pg/ml, BPH=6.8 pg/ml). Levels of VEGF-C were similar in both groups (PCa=832.6 pg/ml, BPH=823.7 pg/ml). In ROC curve, the area under curve (AUC) was 0.70 (95%CI: 0.60-0.80) and the cut-off value for which a higher proportion of patients was correctly classified (20%) was 26.0 pg/mL. Conclusion: Although VEGF-A is increased in cancer prostate patients a statistically significant correlation could not be established in this study. VEGF-C was not found to be a useful biomarker.

• Korean Journal of Head & Neck Oncology
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• v.21 no.1
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• pp.3-9
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• 2005

Purpose: In oral tongue cancer, the degree of tumor invasion has a significant effect on the prognosis. We hypothesized that the destruction of extracelluar matrix and neovascularization are related to tumor infiltration mechanism. By studying the the tissues of early stage oral tongue cancer patients, we are intend to clarify the invasion related factors in oral tongue cancer. Material and Methods: To demonstrate the invasion process in early T-stage oral tongue cancer, the expressions of extracellular matrix destruction related molecules(MMP2, MMP9) and neovascularization related molecule(VEGF) were observed by immunohistochemical study. Also, immunohistochemical staining of CD31 was done for quantification of neovascularization. With the experiment showed above, we analyzed relationship between expression of each substances and tumor invasion depth, tumor free survival rates and cervical lymph node metastasis rate in early T-stage oral tongue cancer. Results: The expression rates of MMP2, MMP9, VEGF in 38 early oral cancer patients were 52.6%, 78.9% 52.6%, respectively. Significant correlation was found between the VEGF expression and microvessel density showed by CD31 immunohistochemical staining(p<0.001). VEGF expressions were significantly related with tumor invasion depth(p=0.002). The tumor free survival rate of those patients with VEGF-positive tumors was significantly poorer than in those with VEGF-negative tumors(p=0.019). Conclusion: This results indicate that VEGF is a useful marker for predicting the tumor invasion in patients with early tongue cancer and could be used as a beneficial factors in defining operative field and prognosis.

• Asian-Australasian Journal of Animal Sciences
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• v.22 no.6
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• pp.788-795
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• 2009

Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis under various physiological and pathological conditions. We found that the VEGF isoforms VEGF120, VEGF164, and VEGF188 were expressed in the bovine mammary gland and bovine mammary epithelial cells (bMECs). Expression of VEGF in the mammary gland was significantly higher during the lactation period than during the dry period. Although dexamethasone or prolactin alone had little effect on the expression of VEGF, that in dexamethasone-treated cells was significantly induced after additional treatment with prolactin. Furthermore, the VEGF expression induced by the combination of dexamethasone and prolactin was reduced by PD98059 in a dose-dependent manner. This combination also stimulated the phosphorylation of p44/p42 MAP kinase in these cells. These results strongly suggest that the combination of dexamethasone and prolactin stimulates VEGF expression in bMECs via p44/p42 MAP kinase.

• Journal of the Korean Applied Science and Technology
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• v.37 no.2
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• pp.354-361
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• 2020

The purpose of this study was to investigate the effects of regular taekwondo training on neurotrophic factors and cognitive function in obese middle-aged women. Thirty-three middle-aged women with obesity were selected for this study and randomly assigned into a control group(CG, n=18) and an taekwondo group(TG, n=15). The TG performed taekwondo training 5 times weekly for 16 weeks, while the CG did not exercise training. Serum brain-derived neurotrophic factor(BDNF), vascular endothelial growth factor(VEGF), and insulin-like growth factor-1(IGF-1) levels were analyzed and Stroop Color and Word tests were performed before and after the intervention. The serum BDNF and IGF-1 levels were significantly increased in the TG after the intervention(p<.05). On the other hand, no statistically significant differences were found in the serum VEGF levels, or in the Stroop Color and Word Test scores(p>.05). These results suggest that regular taekwondo training may be affects levels of peripheral neurotrophic factors but not cognitive function in obese middle-aged women.

• Applied Biological Chemistry
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• v.46 no.1
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• pp.50-54
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• 2003

Polygonum cuspidatum has been used as a fork medicine for a long time. Emodin was purified from the root of P. cuspidatum by thin layer chromatography (TLC) and preparative high perfomance liquid chromatography (HPLC). The effects of emodin on the migration of endothelial cells and in vitro angiogenesis stimulated with vascular endothelial cell growth factor (VEGF) were examined, using human umbilical vein endothelial cells (HUVECs) and porcine pulmonary arterial endothelial cells (PPAECs). Emodin potently inhibited the VEGF-induced migration of (HUVECs) at relatively low cocentrations $(0.1-10\;{\mu}g/ml)$; the inhibition of endothelial cells by emodin was 75.4% at $0.1\;{\mu}g/ml$ and about 90% at $1\;{\mu}g/ml$. Emodin also inhibited VEGF-induced sprout formation in vitro at concentrations of $0.1-10\;{\mu}g/ml$. Emodin was also evaluated for the inhibitory potential on in vivo angiogenesis in a growing chick embryo chorioallantoic membranes (CAM). At a concentration of $1.0\;{\mu}g/ml$ Per disc, emodin was able to induce avacular zone in the CAMs. These findings suggest that emodin is a potent angiogenesis inhibitor and P. cuspidatum is a useful herb in the development of therapeutics for angiogenesis dependent diseases.