• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.42 no.5
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• pp.271-277
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• 2016

Objectives: The objective of this study was to retrospectively investigate the association of diseases having an influence on inhibition of angiogenesis such as hypertension, diabetes mellitus type II, hypercholesterolemia, and rheumatoid arthritis (RA) with the development of osteonecrosis of the jaws. Materials and Methods: The 135 patients were allocated into 4 groups of bisphosphonate-related osteonecrosis of the jaw (BRONJ) group (1A); non-BRONJ group (1B); osteonecrosis of the jaw (ONJ) group (2A); and control group (2B), according to histologic results and use of bisphosphonate. This retrospective study was conducted with patients who were treated in one institute from 2012 to 2013. Fisher's exact test and logistic regression analysis were used to analyze the odds ratios of diseases having an influence on inhibition of angiogenesis for development of ONJ. Results: The effects of diabetes and hypertension were not statistically significant on development of ONJ. When not considering bisphosphonate use, RA exhibited a high odds ratio of 3.23 (P=0.094), while hyperlipidemia showed an odds ratio of 2.10 (P=0.144) for development of ONJ. More than one disease that had an influence on inhibition of angiogenesis showed a statistically significant odds ratio of 2.54 (P=0.012) for development of ONJ. Conclusion: Patients without diseases having an influence on inhibition of angiogenesis were at less risk for developing ONJ.

• 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.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.30 no.5
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• pp.400-405
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• 2004

Angiogenesis inhibition is major concern to cancer chemotherapy and many studies about compound inhibiting angiogenesis is in progression. The long-known preventive effect of plant-based diet on tumorigenesis and other chronic diseases is well documented. Especially soy extract, genistein, is known to be potent angiogenesis inhibitor and prevent development and progression of tumor. In the present study, the effect of angiogenesis on tumorigenesis and chemopreventive effect of genistein by angiogenesis inhibition in hamster buccal pouch oral carcinigenesis model induced by 7.12-dimethylbenza(a)nthracene (DMBA) was studied. Forty eight Syrian Golden young adult hamsters (150-200 gm) were divided into two groups. In control group, 0.5% DMBA in heavy mineral oil was applied to hamster buccal pouch three times a week and in experimental group, 0.1 mg of genistein is administered orally everyday in addition to DMBA application. The animals were euthanized from 2 weeks to 16 weeks with interval of 2 week. H&E staining and immunohistochemistry was performed to evaluate microvessel density by using factor VIII-related antigen and avidin-biotin technique. Microvessels per area was quantified and compared between control and experimental group statistically. The results were as follows. 1. Microvessel density was increased time dependently in both groups and especially the increase was significant from 12 weeks to 16 weeks. 2. When comparing both group, the experimental group showed significantly low microvessel density than control group in 12 weeks (p=0.043), 14 weeks (p=0.050), 16 weeks (p=0.037). Based on these results, it was concluded that genistein influenced oral carcinogenesis by angiogenesis inhibition.

• YAKHAK HOEJI
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• v.37 no.5
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• pp.532-537
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• 1993

Angiogenesis refers to the formation of new capillary blood vessels, or neovascularization occurring under various physical conditions, such as development of the embryo, formation of corpus luteum, wound healing and pathological conditions including tumor growth and metastases, hemangiomas, diabetic retinopathy, rheumatoid arthritis. There are many evidences that angiogenesis is important for the progressive growth of solid tumors and also permits the shedding of metastatic tumors from the primary site. Thus, treatment of angiogenesis inhibitors might be a novel strategy for tumor growth inhibition. Normal vascular endothelial cells are in a state of differentiation and angiogenic endothelial cells migrate and proliferate, and they subsequently differentiate into vessel-forming quiescent phenotype cells, Therfore, it was speculated that a modifier of cell differentiation could also affect angiogenesis. In order to identify new antiangiogenic factors, the research was conducted to estimate the inhibitory activities of cell differentiation agents by means of chick embryo chorioallantoic membrane(CAM) assay. Hence, we have established the CAM assay for the screening of antiangiogenic agents. Using the CAM assay, we found that ursolic acid, a tumor cell differentiation-inducing agent, showed a markedly inhibitory effect on chick embryonic angiogenesis.

• Archives of Pharmacal Research
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• v.25 no.4
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• pp.500-504
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• 2002

Propolis, obtained from honeybee hives, has been used in Oriental folk medicine as an anti-inflammatory, anti-carcinogenic, and immunomodulatory agent. There is considerable evidence suggesting that angiogenesis and chronic inflammation are codependent. Blockage of angiogenesis results in an anti-inflammatory effect. Ethanol (EEP) and ether extracts of propolis (REP), and caffeic acid phenethyl ester (CAPE), an active component of propolis, were examined for their anti-angiogenic activities using the chick embryo chorioallantoic membrane (CAM), and the calf pulmonary arterial endothelial (CPAE) cell proliferation, assays. The presence of EEP, REP and CAPE inhibited angiogenesis in the CAM assay and the proliferation of CPAE cells. The results suggest that anti-angiogenic activities of EEP, REP and CAPE are also responsible for their anti-inflammatory effect.

• 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.

• KSBB Journal
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• v.18 no.1
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• pp.25-29
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• 2003

In this study, we examined the effects of the methanolic extract(CL-ex) of Codonopsis lanceolata on the angiogenesis stimulated with basic fibroblast growth factor(bFGF) in vitro, using porcine pulmonary arterial endothelial cells(PPAECs). In addition, we investigated the endothelial functions involved in angiogenesis, such as proliferation, migration and secretion of matrix metalloproteinases(MMPs), using human umbilical vein endothelial cells(HUVECS). CL-ex inhibited FGF-induced sprout formation in vitro at concentrations of 0.1-100 ug/ml. Although CL-ex did not affect the proliferation of endothelial cells, CL-ex strongly inhibited the FGF-induced migration of HUVECS at concentrations of 0.1-1 ug/ml; the degree of inhibition of endothelial cells by C-ex was 49.4% at 0.1 ug/ml and 71.9 % at 1.0 ug/ml. Moreover, CL-ex inhibited the secretion of MMPs from HUVECS stimulated with FGF. Therefore, the inhibitory effect of CL-ex on angiogenesis in vitro could be explained by the inhibition of endothelial cell migration. From these results, we suggest that Codonopsis lanceolata is a useful herb for the development of therapeutics or preventive food factors for angiogenesis related diseases, such as tumors.

• THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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• v.4 no.1
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• pp.177-197
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• 1998

This experimental study was carried out to evaluate the effect of Yipahnsan on angiogenic inhibition mechanism. This study investigates the effects of Yipahnsan on angiogenic inhibition mechanism evaluate cell adhesive inhibition effect, DNA fragmantaion analysis, nuclear condensation assay, FACScan analysis, angiogenic lumen formation assay, immunocytochemistry analysis, RT-PCR for mRNA expression, western blot analysis, confocal analysis for $Ca^{2+}influx$. The results were summarized as follows : 1. The cell adhesive inhibition ability was strongly increased from $5{\mu}g/ml$ on ECV304 cell line and ECVPAR cell line. 2. YY water extract caused $G_0/G_1$ arrest peak to existed on the ECV304 cell line. 3. YY water extract caused inhibition of proliferation and inducement of apoptosis on the collagen coated plate in ECV304 cell line. 4. YY water extract inhibited the lumen formation on the matrigel coated plate in ECV304 cell line. 5. YY water extract inhibited the expressions of LFA-1 and ELAM-1 on ECV304 cell line and ECVPAR cell line. 6. YY water extract inhibited the expressions of MMP-9 and uPA on ECV304 cell line and ECVPAR cell line. 7. YY water extract inhibited the expression of integrin ${\alpha}_v{\beta}_3$ on ECV304 cell line and ECVPAR cell line. 8. YY water extract decreased the change of $Ca^{2+}$ in intracellular on ECV304 cell line and ECVPAR cell line. According to the results, Yipahnsan showed to be a key antagonist of integrin ${\alpha}_v{\beta}_3$, and to be induction of apoptosis by p53 through flow cytometry. This report also demonstrated that expressions of MMP-9 and uPA were blocked under the angiogenesis model. Thus, we suggested that Yipahnsan blocks angiogenesis by inducing apoptosis in ECV304 and ECVPAR cell lines, and another oriental herbal medicine that treats qi-stagnation and blood-stasis type also has angiogenic inhibition effects.

• THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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• v.4 no.1
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• pp.17-36
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• 1998

This experimental study was carried out to evaluate the effects of Hwallakhyoreungdan on angiogenic inhibition mechanism. In order to investigate the effects of Hwallakhyoreungdan on angiogenic inhibition mechanism, MTT assay, cell adhesive inhibition effect, DNA fragmantaion analysis, Nuclear condensation assay, FACScan analysis, Angiogenic lumen formation assay, Immunocytochemistry analysis, RT-PCR for mRNA expression, Western blot analysis and Confocal analysis for $Ca^{2+}$ change were performed. The results were summarized as follows: 1. The cell adhesive inhibition ability was strong from $5{\mu}g/ml$. 2. The $G_0/G_1$ arrest peak was existed on ECV304 cell-line. 3. The cells on Collagen plate were inhibition of proliferation and inducement of apoptosis by HR water extract. 4. Angiogenic lumen formation was inhibited by HR water extract. 5. LFA-1 and ELAM-1's expression were inhibited by HR water extract. They are commenly participation on inflammation and tumor regeneration. 6. The expression of MMP-9 and uPA were inhibited by HR water extract. 7. The expression of integrin ${\alpha}_v{\beta}_3$ was inhibited by HR water extract. 8. The expression of intracellular molecule were successively inhibited by HR water extract therefore the proliferation of ECV304 cell line was stopped and apoptosis was induced. 9. The change of $Ca^{2+}$ was decreased by HR water extract it cause confusion of signal transduction pathway therefore it was take part in apoptosis. According to the results, Hwallakhyoreungdan showed to be a key antaonist of integrin ${\alpha}_v{\beta}_3$, and to be induction of apoptosis by p53 through flow cytometry. This report also demonstrated that expressions of MMP-9 and uPA was blocked under the angiogenesis model. Thus, we suggests that Hwallakhyoreungdan blocks angiogenesis by inducing apoptosis of ECV304 and ECVPAR cell lines and another oriental herbal medicine that treats blood-stasis type also has angiogenic inhibition effects.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.4
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• pp.327-334
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• 2015

The cytoprotective enzyme heme oxygenase-1 (HO-1) influences endothelial cell survival, proliferation, inflammatory response, and angiogenesis in response to various angiogenic stimuli. In this study, we investigate the involvement of HO-1 in the angiogenic activity of orexin-A. We showed that orexin-A stimulates expression and activity of HO-1 in human umbilical vein endothelial cells (HUVECs). Furthermore, we showed that inhibition of HO-1 by tin (Sn) protoporphryin-IX (SnPP) reduced orexin- A-induced angiogenesis in vivo and ex vivo. Orexin-A-stimulated endothelial tube formation and chemotactic activity were also blocked in SnPP-treated vascular endothelial cells. Orexin-A treatment increased the expression of nuclear factor erythroid-derived 2 related factor 2 (Nrf2), and antioxidant response element (ARE) luciferase activity, leading to induction of HO-1. Collectively, these findings indicate that HO-1 plays a role as an important mediator of orexin-A-induced angiogenesis, and provide new possibilities for therapeutic approaches in pathophysiological conditions associated with angiogenesis.