• Asian Pacific Journal of Cancer Prevention
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• v.14 no.1
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• pp.63-68
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• 2013

Background: Tumor angiogenesis correlates with recurrence and appears to be a prognostic factor for both breast and prostate cancers. In the present study, we aimed to investigate the correlation of microvessel density (MVD), a measure of angiogenesis, with nuclear pleomorphism, mitotic count, and vascular invasion in breast and prostate cancers at preclinical and clinical levels. Methods: Samples from xenograft tumors of luminal B breast cancer and prostate adenocarcinoma, established by BT-474 and PC-3 cell lines, respectively, and commensurate human paraffin-embedded blocks were obtained. To determine MVD, specimens were immunostained for CD-34. Nuclear pleomorphism, mitotic count, and vascular invasion were determined using hematoxylin and eosin (H&E)-stained slides. Results: MVD showed significant correlations with nuclear pleomorphism (r=0.68, P=0.03) and vascular invasion (r=0.77, P=0.009) in breast cancer. In prostate cancer, MVD was significantly correlated with nuclear pleomorphism (r=0.75, P=0.013) and mitotic count (r=0.75, P=0.012). In the breast cancer xenograft model, a significant correlation was observed between MVD and vascular invasion (r=0.87, P=0.011). In the prostate cancer xenograft model, MVD was significantly correlated with all three parameters (nuclear pleomorphism, r=0.95, P=0.001; mitotic count, r=0.91, P=0.001; and vascular invasion, r=0.79, P=0.017; respectively). Conclusions: Our results demonstrate that MVD is correlated with nuclear pleomorphism, mitotic count, and vascular invasion at both preclinical and clinical levels. This study therefore supports the predictive value of MVD in breast and prostate cancers.

• Tuberculosis and Respiratory Diseases
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• v.48 no.5
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• pp.757-765
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• 2000

Background : Angiogenesis plays a critical role in human tumor growth and metastasis. Microvessel count as a measure of tumor angiogenesis, has been significantly correlated with invasive and metastatic patterns in breast. prostate and cutaneous carcinomas. Materials and Methods : Fifty patients with curatively resected non-small cell lung cancer were evaluated. Tumor tissues embedded in paraffin block were stained by anti CD 31 (PECAM, platelet endothelial cellular adhesion molecule) using immunohistochemical method to assess microvessel count. Microvessels were counted in the most active areas of neovascularization(microscopy, 200$\times$). Results: 1) Mean microvessel count was 47.1$\pm$17.7(per 200$\times$field) in total 50 cases. 2) Mean microvessel count of adenocarcinoma (54.4$\pm$19.9) was significantly higher than that of squamous cancer (43.9$\pm$16.2) (p<0.05), but there were no relationship between microvessel count and TNM stages. 3) Median survival time, 2-year and 5-year survival rates of the low microvascular group (microvessel count<45, 22 cases) were 61 months, 80% and 40%, respectively, and those of the high microvascular group(microvessel count$\geq$45, 28 cases) were 46 months, 75% and 12%, respectively. As results, prognosis of low microvascular group is statistically significantly superior to that of the high microvascular group (p=0.0162, Kaplan-Meier, log-rank). Conclusion : Angiogenesis assessed by microvessel count can be used as one of the significant prognostic factors in non-small cell lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.43 no.6
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• pp.894-902
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• 1996

Background : Tumor angiogenesis is the growth of new vessels toward and within tumor. It has been demonstrated that the growth of tumor beyond a certain size requires angiogenesis and it is closely involved in tumor progression and metastasis. The finding that intensity of neovascularization correlates independently with metastasis may lead to identification of patients in whom radical surgery should be supplemented by systemic treatment. Method : We have collected paraffin blocks of bronchoscopic biopsy of patients with non-small cell lung cancer. We highlighted the vessel by staining endothelial cell with JC70 monoclonal antibody(to CD31) immunohistochemically and counted microvessels under 200 X field using light microscopy. Results : 1) The mean microvessel count was $32.7{\pm}20.8$ (9-96) in total 29 cases. 2) There were no correlations between microvessel counts and pathologic cell type, T staging, node melastasis(N) and hematogenous metastasis(M) (p>0.05). 3) The median follow-up duration was 15 months(2-46) and there was no correlation between the microvessel counts and survival rate of lung cancer patients (p>0.05). Conclusion : Tumor angiogenesis seems to be an important prognostic factor suggesting the probability of metastasis. But the microvessel count in the bronchoscopic biopsy specimen was inadequate and very limited. There has been no data about angiogenesis of lung cancer in korea yet So the study of tumor angiogenesis using resected lung tumor specimen would be demanded.

• Journal of Gastric Cancer
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• v.2 no.4
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• pp.195-199
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• 2002

Purpose: Angiogenesis is essential for tumor growth and metastasis and depends on the production of angiogenic factors that are secreted by tumor cells. Vascular endothelial growth factor (VEGF) is the most significant angiogenic factor and a selective mitogen for endothelial cells. VEGF, also known as the vascular permeability factor, acts on endothelial cells to increase microvascular permeability and directly stimulate the growth of new blood vessels. Several studies have reported that the expression of VEGF is correlated with hematogenous recurrence via angiogenesis in gastric carcinomas. This research evaluated the relationship between the expression of VEGF and hepatic and peritoneal recurrence in gastric carcinomas. Materials and Methods: Thirty specimens resected from patients with primary gastric carcinomas who had undergone curative resections were divided into three group: Group I, early gastric carcinomas without recurrence; Group II, advanced gastric carcinomas with hepatic recurrence; and Group III, advanced gastric carcinomas with peritoneal recurrence. The expression of VEGF and the density of the microvessel count were examined using immunohistochemistry. Results: 1) The expression of VEGF in Group II and Group III ($63.2\pm\24.3\%$) was stronger than that in Group I ($7\pm\4.2\%$). The expression of VEGF in Group II ($76.5\pm\13.2\%$) was stronger than that of the Group III ($50\pm\14.2\%$) (P<0.05). 2) The microvessel count in Group II ($49.9\pm14.5$) was more than that in Group I ($8.6\pm2.6$) and Group III ($29.1\pm18.1$) (P<0.05). 3) The microvessel count was increased significantly with increasing the expression of VEGF. Conclusions: The expression of VEGF is associated with advanced stomach cancer and hepatic recurrence has a higher expression of VEGF than peritoneal recurrence with neovascularization. Thus the expression of VEGF can be considered to be a useful indicator of recurrence in gastric carcinoma and especially in hepatic recurrence.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.3
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• pp.1187-1192
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• 2014

Background: To correlate breast cancer subtypes with prognostic factors, microvessel density (MVD), vascular endothelial growth factor (VEGF) expression and clinical features. Materials and Methods: One hundred cases of primary breast carcinoma were classified using biomarkers on tissue microarray as: luminal A [estrogen receptor (ER)+, HER2-, $Ki-67{\leq}14%$], luminal B [ER+, HER2+ or ER+, HER2-, Ki-67>14%], HER2, triple negative basal-like (TNB) [any basal cytokeratins (CKs, 5, 14, 17) and/or endothelial growth factor receptor (EGFR) expression], and TN without such markers [TNN, null], and assessed for p53, vimentin, VEGF and CD31 immunoperoxidase. Results: Of the 100 cases (mean age, 51 years; mean tumor size, 3.2cm; 56% with nodal metastasis; 89 invasive ductal carcinomas, not otherwise specified, 4 invasive lobular carcinomas, 3 metaplastic carcinomas, and 4 other types) there were 39 luminal A, 18 luminal B, 18 HER2, 15 TNB and 10 TNN. The positivities of basal-like markers in the basal-like subtype were 78.3% for CK5, 40% for CK14, 20% for CK17, 46.7% for EGFR. There was no significant difference in age distribution, tumor size, degree of tubular formation, pleomorphism, lymphovascular invasion, nodal metastasis, MVD, VEGF expression and survival among subgroups. TNs demonstrated significantly higher tumor grade, mitotic count, Ki-67 index, p53 and vimentin and decreased overall survival compared with nonTN. Conclusions: The distribution of breast cancer subtypes in this study was similar to other Asian countries with a high prevalence of TN. The high grade character of TN was confirmed and CK5 expression was found to be common in our basal-like subtype. No significant elevation of MVD or VEGF expression was apparent.

• Archives of Plastic Surgery
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• v.34 no.5
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• pp.551-556
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• 2007

Purpose: Pseudomonas aeruginosa is an etiologic agent in serious wound infection. Pseudomonas aeruginosa infection is problematic because this organism is resistant to many antimicrobial drugs. The purpose of this study was to compare the bactericidal effect of commonly used topical agents and their effect on wound healing. Methods: Pseudomonas aeruginosa-infected full-thickness skin defect was developed on the mouse to compare 3 commonly used topical agents-Betadine, 2% Gentamicin solution and 0.3% Acetic acid with the control group. Wound size change, bacterial colony counts and histologic findings of each groups were analyzed. Results: The wound size decreased in all treated groups as compared with the control group. However, there was no statistical difference. Gentamicin solution group was showed the lowest bacterial colony count and statistically significant difference compared with the control group(p=0.032). Other treated groups were also effective against Pseudomonas aeruginosa, but not different statistically. Histologic findings revealed that epithelialization, granulation tissue formation and microvessel proliferation were increased and necrosis and inflammation were decreased in all treated groups compared to the control group, but not different statistically. Betadine group significantly increased granulation tissue formation compared to the control group (p= 0.041). Conclusion: There is no universal topical agent that enhances most aspects of wound healing while simultaneously decreasing the bacterial concentration. However, Gentamicin solution may be an optimal topical agent for Pseudomonas aeruginosa infected wound. Further study should experiment on human with Gentamicin solution to confirm a effect on Pseudomonas aeruginosa infected wound for clinical applications.

• Nutrition Research and Practice
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• v.8 no.4
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• pp.377-385
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• 2014

BACKGROUND/OBJECTIVES: Abundant consumption of seaweeds in the diet is epidemiologically linked to the reduction in risk of developing cancer. In larger cases, however, identification of particular seaweeds that are accountable for these effects is still lacking, hindering the recognition of competent dietary-based chemo preventive approaches. The aim of this research was to establish the antiproliferative potency and angiosuppressive mode of action of Stoechospermum marginatum seaweed methanolic extract using various experimental models. MATERIALS/METHODS: Among the 15 seaweeds screened for antiproliferative activity against Ehrlich ascites tumor (EAT) cell line, Stoechospermum marginatum extract (SME) was found to be the most promising. Therefore, it was further investigated for its anti-proliferative activity in-vitro against choriocarcinoma (BeWo) and non-transformed Human embryonic kidney (HEK 293) cells, and for its anti-migratory/tube formation activity against HUVEC cells in-vitro. Subsequently, the angiosuppressive activity of S. marginatum was established by inhibition of angiogenesis in in-vivo (peritoneal angiogenesis and chorioallantoic membrane assay) and ex-vivo (rat cornea assay) models. RESULTS: Most brown seaweed extracts inhibited the proliferation of EAT cells, while green and red seaweed extracts were much less effective. According to the results, SME selectively inhibited proliferation of BeWo cells in-vitro in a dose-dependent manner, but had a lesser effect on HEK 293 cells. SME also suppressed the migration and tube formation of HUVEC cells in-vitro. In addition, SME was able to suppress VEGF-induced angiogenesis in the chorio allantoic membrane, rat cornea, and tumor induced angiogenesis in the peritoneum of EAT bearing mice. A decrease in the microvessel density count and CD31 antigen staining of treated mice peritoneum provided further evidence of its angiosuppressive activity. CONCLUSIONS: Altogether, the data underline that VEGF mediated angiogenesis is the target for the angiosuppressive action of SME and could potentially be useful in cancer prevention or treatment involving stimulated angiogenesis.

• Tuberculosis and Respiratory Diseases
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• v.50 no.5
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• pp.557-567
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• 2001

Background : Tumor angiogenesis is required for tumor growth and metastasis. In this study, we investigated the correlation between the intensity of angiogenesis and stage, nodal status, histologic type, metastasis and survival rate of non-small cell lung cancer. Method : Formalin fixed, paraffin embedded surgical specimens of 45 patients who had surgically resected primary non-small cell lung cancers without pre or post operative adjuvant chemotherapy or radiotherapy were examined. The microvessel count(MVC) was demonstrated by immunohistochemical staining for CD31(platelet endothelial cell adhesion molecule, PECAM). Results : Microvessel counts(MVCs) in stage IIIA and IIIB were higher than in stage I and II(p<0.05). The MVC in patients with lymph node metastasis was higher than that in patients without lymph node metastasis, although the difference was not statistically significant(p>0.05). However, in adenocarcinoma, the MVC in patients with lymph node metastasis was significantly higher than that seen in patients without lymph node metastasis(p<0.05). The MVC in adenocarcinoma was higher than that in squamous cell carcinoma(p<0.05). The difference between the MVCs of adenocarcinoma and squamous cell carcinoma was not statistically significant in stage I and II or N0 stage(p>0.05). However, in stage IIIA and IIIB or N1~3 stage, the MVC in adenocarcinoma was higher than that in squamous cell carcinoma(p<0.05). MVC was more increased when metastasis developed within 12 months. In the same histologic type and stage, the duration of survival time in patients with high MVC was shorter than in patients with low MVC, however the difference was not statistically significant(p>0.05). The survival rate in patients with high MVCs was lower than that in patients with low MVCs(P<0.05). Conclusion : In non-small cell lung cancer, MVC correlated relatively well with pathologic stage, nodal status(limited in patients with adenocarcinoma), histologic type, postoperative metastasis and survival rate. However, in the same histologic type and stage, MVC was not significantly related to the duration of survival. Therefore the assessment of the intensity of angiogenesis in non-small cell lung cancer may be helpful in predicting prognosis and in selecting patients for systemic adjuvant therapy of potential metastasis according to the results.

• Korean Journal of Head & Neck Oncology
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• v.20 no.2
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• pp.135-142
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• 2004

Objectives: The purpose of this study was to evaluate for prognostic significance of VEGF expression and tumor angiogenesis in papillary carcinomas of the thyroid. Materials and Methods: The materials were 79 cases of papillary thyroid carcinomas, and age, sex, tumor size, multiplicity of tumor, capsular invasion, lymph node metastasis, recurrence, TNM stage, DeGroot stage and AMES scale were evaluated. An immunohistochemical stains for CD 34 to estimate microvessel density (MVD), and VEGF were done. MVD was defined as an average count of vessels per ${\times}400$ power field in the most vascularized area. VEGF expression was interpreted as 1+ and 2+ according to staining intensity and percentages of positive cells. Results: Mean score of MVD was $39.7{\pm}16.9.$ MVD were significantly higher in cases with capsular invasion (p=0.0001), lymph node metastasis (p=0.0001), TNM stage III (p=0.0022), DeGroot stage III (p=0.0163) and high risk group by AMES scale (p=0.0001). VEGF 2+ expression rate was significantly increased in cases with capsular invasion and lymph node metastasis (p=0.0006, p=0.0013), and in cases with TNM stage III, DeGroot stage III and high risk group by AMES scale (p=0.0236, p=0.0003, p=0.0293). In VEGF 2 + expression group, MVD was significantly higher than in VEGF 1 + group (p=0.0008), and MVD showed positive relation to VEGF 2 + expression (r=0.4616). Conclusion: VEGF expression and high MVD were significantly correlated to capsular invasion, lymph node metastasis, TNM stage III, DeGroot stage III and high risk group by AMES scale. The expression of VEGF and high MVD could be considered to be one of prognostic factor in papillary thyroid carcinomas.

• Ultrasonography
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• v.32 no.2
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• pp.132-142
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• 2013

Purpose: The purpose of this study is to investigate the correlations of various kinetic parameters derived from the time intensity curve in a xenograft mouse model injected with a prostate cancer model (PC-3 and LNCaP) using an ultrasound contrast agent with histopathologic parameters. Materials and Methods: Twenty nude mice were injected with human prostate cancer cells (15 PC-3 and five LNCaP) on their hind limbs. A bolus of $500{\mu}L$ ($1{\times}10^8$ microbubbles) of second-generation US contrast agent (SonoVue) was injected into the retroorbital vein. The region of interest was drawn over the entire tumor. The time intensity curve was acquired and then fitted to a gamma variate function. The maximal intensity (A), time to peak (Tp), maximal wash-in rate (washin), washout rate (washout), area under the curve up to 50 sec ($AUC_{50}$), area under the ascending slope ($AUC_{in}$), and area under the descending slope ($AUC_{out}$) were derived from the parameters of the gamma variate fit. Immunohistochemical staining for VEGF and CD31 was performed. Tumor volume, the area percentage of VEGF stained in a field, and the count of CD31 (microvessel density, MVD) positive vessels showed correlation with the parameters from the time intensity curve. Results: No significant differences were observed between the kinetic and histopathological parameters from each group. MVD showed positive correlation with A (r=0.625, p=0.003), washin (r=0.462, p=0.040), $AUC_{50}$ (r=0.604, p=0.005), and $AUC_{out}$ (r=0.587, p=0.007). Positive correlations were also observed between tumor volume and $AUC_{50}$ (r=0.481, p=0.032), washin (r=0.662, p=0.001), and $AUC_{out}$ (r=0.547, p=0.012). Washout showed negative correlations with MVD (r=-0.454, p=0.044) and tumor volume (r=-0.464, p=0.039). The area percentage of VEGF did not show any correlation with calculated data from the curve. Conclusion: MVD showed correlations with several of the kinetic parameters. CEUS has the potential for prediction of tumor vascularity in a prostate cancer animal model.