• Preventive Nutrition and Food Science
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• v.19 no.4
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• pp.299-306
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• 2014

Hesperetin has been shown to possess a potential anti-angiogenic effect, including vascular formation by endothelial cells. However, the mechanisms underlying the potential anti-angiogenic activity of hesperetin are not fully understood. In the present study, we evaluated whether hesperetin has anti-angiogenic effects in human umbilical vascular endothelial cells (HUVECs). HUVECs were treated with 50 ng/mL vascular endothelial growth factor (VEGF) to induce proliferation as well as vascular formation, followed by treatment with several doses of hesperetin (25, 50, and $100{\mu}M$) for 24 h. Cell proliferation and vascular formation were analyzed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and tube formation assay, respectively. In addition, cell signaling related to cell proliferation and vascular formation was analyzed by western blot. Furthermore, a mouse aorta ring assay was performed to confirm the effect of hesperetin on vascular formation. Hesperetin treatment did not cause differences in HUVECs proliferation. However, hesperetin significantly inhibited VEGF-induced cell migration and tube formation of HUVECs (P<0.05). Moreover, hesperetin suppressed the expression of ERK, p38 MAPK, and PI3K/AKT in the VEGF-induced HUVECs. In an ex vivo model, hesperetin also suppressed microvessel sprouting of mouse aortic rings. Taken together, the findings suggest that hesperetin inhibited vascular formation by endothelial cells via the inhibition of the PI3K/AKT, ERK and p38 MAPK signaling.

• Korean Journal of Oriental Medicine
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• v.4 no.1 s.4
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• pp.129-138
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• 1998

Angiogenesis, the formation of new blood vessels, is considered to be involved in many pathological symptoms such as diabetic retinopathy, arthritis, inflammation and solid tumour. In particular, it is thought that angiogenesis is critical for development and growth of solid tumour. Recent study shows that there is a highly significant association of microvessel density with overall survival and relapse-free survival in patients with breast tumour In this study, the inhibition effect of angiogenesis of traditional herbs used for the treatment of cancer was examined. It was found out that the extract of Agaricus blazei by boiling water is a possible inhibitor of angiogenesis. It inhibited normal developmental angiogenesis In the chorioallantoic membrane of chick embryos and also inhibited capillary-like tube formation by endotherial cells on matrigel in vitro. These results suggest that Agaricus blazei can be a potent angiogenesis inhibitor.

• The Journal of Korean Institute of Information Technology
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• v.17 no.5
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• pp.77-82
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• 2019

Diabetic retinopathy is a complicated form of diabetes due to circulatory disorder in the peripheral blood vessels of the retina. We segment the microvessel for diagnosing diabetic retinophathy. The conventional methods using filter and features can segment the thick blood vessels, but it has relatively weak for segmenting fine blood vessels. In pre-processing step, noise reduction filter and histogram equalization are applied to suppress the noise and enhance the image contrast. Then, deep learning technique is used for pixel-by-pixel segmentation. The accuracy of conventional methods is between 90% to 94%, while the proposed method has improved as 95% accuracy. There is a problem of segmentation error around the optic disc and exudate due to the network depth. However the accuracy can be improved by modifying the network architecture in the future.

• 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.

• BMB Reports
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• v.46 no.5
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• pp.252-257
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• 2013

Fibroblast activation protein (FAP) is a specific serine protease expressed in tumor stroma proven to be a stimulatory factor in the progression of some cancers. The purpose of this study was to investigate the effects of FAP knockdown on tumor growth and the tumor microenvironment. Mice bearing 4T1 subcutaneous tumors were treated with liposome-shRNA complexes targeting FAP. Tumor volumes and weights were monitored, and FAP, collagen, microvessel density (MVD), and apoptosis were measured. Our studies showed that shRNA targeting of FAP in murine breast cancer reduces FAP expression, inhibits tumor growth, promotes collagen accumulation (38%), and suppresses angiogenesis (71.7%), as well as promoting apoptosis (by threefold). We suggest that FAP plays a role in tumor growth and in altering the tumor microenvironment. Targeting FAP may therefore represent a supplementary therapy for breast cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.22
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• pp.9805-9812
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• 2014

Radixin, a member of the ERM (ezrin-radixin-moesin) family, plays important roles in cell motility, invasion and tumor progression. It is expressed in a variety of normal and neoplastic cells, including many types of epithelial and lymphoid examples. However, its function in glioblastomas remains elusive. Thus, in this study, radixin gene expression was first examined in the glioblastoma cells, then suppressed with a lentivirus-mediated short-hairpin RNA (shRNA) method.We found that there were high levels of radixin expression in glioblastoma U251cells. Radixin shRNA caused down-regulation of radixin gene expression and when radixin-silenced cells were implanted into nude mice, tumor growth was significantly inhibited as compared to blank control cells or nonsense shRNA cells. In addition, microvessel density in the tumors was significantly reduced. Thrombospondin-1 (TSP-1) and E-cadherin were up-regulated in radixin- suppressed glioblastoma U251 cells. In contrast, MMP9 was down-regulated. Taken together, our findings suggest that radixin is involved in GBM cell migration and invasion, and implicate TSP-1, E-cadherin and MMP9 as metastasis-inducing factors.

• Journal of Chest Surgery
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• v.32 no.2
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• pp.158-163
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• 1999

Background: The author studied to define the current indications for surgical management of chest tuberculosis and to analyze the results of the operative procedures. Material and Method: The records of 87 patients among 107 patients operated on between January 1992 and May 1995 were reviewed. These patients were divided into 4 groups. Group I patients (n=45) underwent decortication with or without wedge resection of the lesion. Group II patients(n=23) underwent radical curettages of chest wall involving rib caries with or without thoracotomy. Group III patients(n=12) underwent standard pneumonectomy or pleuropneumonectomy. Group IV patients(n=7) underwent exploratory thoracotomy or wedge resection of tuberculous lung lesion. Result: Statistical analysis revealed an inverse correlation between AIs and intratumoral microvessel densities in squamous cell lung carcinoma(Spearman rank correlation coefficient r=- 0.229, p=0.047). Conclusion: The author concludes that surgery for chest tuberculosis is the definite management for therapeutic indications and surgical radication of tuberculous carriers for management of chest tuberculosis is safe and has satisfactory results.

• BMB Reports
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• v.53 no.11
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• pp.600-604
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• 2020

Macrophages are re-educated and polarized in response to myocardial infarction (MI). The M2 anti-inflammatory phenotype is a known dominator of late stage MI. Mesenchymal stem cells (MSCs) represent a promising tool for cell therapy, particularly heart related diseases. In general, MSCs induce alteration of the macrophage subtype from M1 to M2, both in vitro and in vivo. We conjectured that hypoxic conditions can promote secretome productivity of MSCs. Hypoxia induces TGF-β1 expression, and TGF-β1 mediates M2 macrophage polarization for anti-inflammation and angiogenesis in infarcted areas. We hypothesized that macrophages undergo advanced M2 polarization after exposure to MSCs in hypoxia. Treatment of MSCs derived hypoxic conditioned medium (hypo-CM) promoted M2 phenotype and neovascularization through the TGF-β1/Smad3 pathway. In addition, hypo-CM derived from MSCs improved restoration of ischemic heart, such as attenuating cell apoptosis and fibrosis, and ameliorating microvessel density. Based on our results, we propose a new therapeutic method for effective MI treatment using regulation of macrophage polarization.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6415-6421
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• 2012

Background: Canine mammary gland tumors (CMGTs) are the most common tumor found in bitches. Changes in HER-2/neu genes in human breast cancer (HBC) lead to decrease in disease-free survival (DFS) and overall survival rate (OSR). Previous studies have demonstrated that the biological behavior of malignant mammary gland tumors (MMGTs) is similar to that of HBC. The present study aimed at evaluating the relationship between overexpression of HER-2/neu and clinicopathological features in MMGTs to represent a model of prognostic factors for HBC. Materials and Method: The clinicopathological data of 35 MMGTs were obtained. Immunohistochemical staining with HER-2, Ki-67 and CD34 markers was conducted with sections from paraffin-embedded blocks. According to standard protocols, histological type, grade, margin status, lymphovascular invasion (LVI), HER-2/neu score, proliferation rate and microvessel density (MVD) of tumors were determined and the association of HER-2/neu overexpression with these parameters was assessed statistically. Results: The IHC results showed that 12 (34.3%) cases were HER-2/neu positive. Statistical analyses indicated a significant relationship between HER-2 positivity and tumor grade (p=0.043), which also was demonstrated with cancer stage (p=0.035), tumor margin involvement (p=0.016), proliferation index (p=0.001) and MVD (p=0.001); however, there was no statistical relationship between LVI and tumor size. Overexpression of the HER-2/neu gene in MMGTs results in similar biological behavior as that of HBC; as a result, these tumors have can be considered to have important similarities in clinicopathological characteristics. Conclusions: MMGTs can be regarded as an HBC animal model. Further studies in this field would result in new treatments that could be beneficial for both dogs and humans.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3857-3862
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• 2012

A total of 96 cases of invasive breast ductal carcinoma were examined for immunohistochemical expression of Bax and Bcl-2 in the epithelial tumor cells and endothelial cells of the blood vessels. We also investigated the association between both proteins in the epithelium in relation to tumor characteristics such as tumor size, grade, lymph node involvement, microvessel density (MVD), hormonal receptors expression and c-erbB-2 overexpression. Bax expression showed a significant association between tumor and endothelial cells (p<0.001) while Bcl-2 expression in tumor cells was inversely associated with that in the endothelial cells (p<0.001). Expression of Bcl-2 in tumor cells was strongly associated with expression of estrogen and progesterone receptors (p=0.003 and p=0.004, respectively). In addition, intratumoral MVD was significantly higher than peritumoral MVD (p<0.001) but not associated with Bax or Bcl-2 expression and other tumor characteristics. We concluded that the number of endothelial cells undergoing apoptosis was in direct linkage with the number of apoptotic tumor cells. Anti-apoptotic activity of the surviving tumor cells appears to propagate cancer progression and this was influenced by the hormonal status of the cells. Tumor angiogenesis was especially promoted in the intratumoral region and angiogenesis was independent of anti-apoptotic activity.