• Proceedings of the Korean Society for Applied Microbiology Conference
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• 2004.06a
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• pp.180-184
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• 2004

• Journal of Microbiology and Biotechnology
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• v.1 no.3
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• pp.163-168
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• 1991

A new angiogenesis inhibitor, FR-118487 was obtained by chemical modification of FR-111142 which was isolated from the fermentation products of Scolecobasidium arenarium F-2015. The antiangiogenic activity of FR-118487 was compared with that of the parent compound, FR-111142. In the endothelial cell proliferation test in vitro and the angiogenesis in the chick embryo chorioal-lantoic membrane assay, FR-118487 had about 5∼10 times stronger antiangiogenic activities than FR-111142. In addition, FR-118487 inhibited the angiogenesis in the rabbit corneal assay and suppressed the solid tumor growth in mice. These findings showed that FR-118487 would be a unique antiangiogenic agent with promising antitumor activity.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7785-7792
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• 2014

Background: Valproic acid (VPA) is a potent anticancer and antiangiogenic agent. However, design and synthesis of chemical derivatives with improved antiangiogenic and anticancer activities are still necessary. In this study a library of novel derivatives of VPA was synthesized and tested. Methods: A human liver cancer cell line (HepG2) and a human normal embryonic kidney cell line (HEK 293) were exposed to various concentrations of VPA derivatives for 24 hours and cell viability was checked by MTT colorimetric assay. Anti-angiogenic properties were evaluated in transgenic zebrafish embryos. Results: N-valproylglycine derivatives suppressed survival almost 70% (p value 0.001) in HepG2 cells but only 10-12% in HEK 293 cells (p value 0.133). They also suppressed angiogenic blood vessel formation by 80% when used between $2-20{\mu}M$ in zebrafish embryos. Valproic acid hydrazides showed moderate level of anticancer activity by affecting 30-50% (p value 0.001) of cell viability in HepG2 cells and 8-10% in HEK293 cells (p value 0.034). Conclusion: The majority of compounds in this study showed potent and stronger antiangiogenic and anticancer activity than VPA. They proved selectively toxic to cancer cells and safer for normal cells. Moreover, these compounds inhibited developmental angiogenesis in zebrafish embryos. Based on the fact that liver is a highly vascularized organ, in case of liver carcinoma these compounds have the potential to target the pathological angiogenesis and could be an effective strategy to treat hepatocellular carcinoma.

• Journal of Microbiology and Biotechnology
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• v.17 no.8
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• pp.1338-1343
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• 2007

Angiogenesis is an essential step in tumor progress and metastasis. Accordingly, small molecules that inhibit angiogenesis would appear to be a promising way to cure angiogenesis-related diseases, including cancer. In the present study, we report that streptochlorin, a small molecule from marine actinomycete, exhibits a potent antiangiogenic activity. The compound potently inhibited endothelial cell invasion and tube formation stimulated with vascular endothelial cell growth factor (VEGF) at low micromolar concentrations where it showed no cytotoxicity to the cells. In addition, streptochlorin inhibited TNF-${\alpha}$-induced $NF-{\kappa}B$ activation in the newly developed cell-based reporter gene assay. These data demonstrate that streptochlorin is a new inhibitor of $NF-{\kappa}B$ activation and can be a basis for the development of novel anti-angiogenic agents.

• 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.

• Proceedings of the PSK Conference
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• 2002.04a
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• pp.109.2-110
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• 2002

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.7
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• pp.3113-3121
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• 2014

Colorectal cancer remains one of the most common types of cancer and a leading cause of cancer death worldwide. In this study, we aimed to investigate effects of DuP-697, an irreversible selective inhibitor of COX-2 on colorectal cancer cells alone and in combination with a promising new multi-targeted kinase inhibitor E7080. The HT29 colorectal cancer cell line was used. Real time cell analysis (xCELLigence system) was conducted to determine effects on colorectal cell proliferation, angiogenesis was assessed with a chorioallantoic membrane model and apoptosis was determined with annexin V staining. We found that DuP-697 alone exerted antiproliferative, antiangiogenic and apoptotic effects on HT29 colorectal cancer cells. For the antiproliferative effect the half maximum inhibition concentration ($IC_{50}$) was $4.28{\times}10^{-8}mol/L$. Antiangiogenic scores were 1.2, 0.8 and 0.5 for 100, 10 and 1 nmol/L DuP-697 concentrations, respectively. We detected apoptosis in 52% of HT29 colorectal cancer cells after administration of 100 nmol/L DuP-697. Also in combination with the thyrosine kinase inhibitor E7080 strong antiproliferative, antiangiogenic and apoptotic effects on HT29 colorectal cancer cells were observed. This study indicates that DuP-697 may be a promising agent in the treatment of colorectal cancer. Additionally the increased effects observed in the combination with thyrosine kinase inhibitor give the possibility to use lower doses of DuP-697 and E7080 which can avoid and/or minimize side effects.

• Advances in pediatric surgery
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• v.8 no.2
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• pp.101-106
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• 2002

The antiangiogenic effects of novel agent KJ3, Betulinic acid, and Fumagillin on the neovascularization were studied by examining ultrastructural alterations in the vasculature of synthetic gelform and mouse neuroblastoma C1300. Small pieces of gelform with 0.4% agar were introduced subcutaneously (s.c.) in 7 week old male CH3/HeJ mice. After the $LD_{50}s$ were determined by FACS analysis, a third of $LD_{50}$ of three drugs were injected either locally or intraperitoneally every other day for 14 days. A/J mice were inoculated s.c. with the C1300 neuroblastoma cell line, then either saline or three drugs were injected in the same manner. The antiangiogenic effects of three drugs were studied by measuring the histologic changes in tumors, and immunostaining for CD34, VIII/vWF, CD105, and thymidine phosphorylase. In the drug treated groups, the number of vessels in gelform experiments and C1300 neuroblastoma experiments were lower than the corresponding values in the control. The histologic findings were significantly different in drug treated groups on day 7, but these were not significant on day 14. These results imply that antiangiogenic agents were effective when the tumor burden is minimal.

• Journal of Microbiology and Biotechnology
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• v.12 no.4
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• pp.702-705
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• 2002

Apicularen A (Api A) was recently isolated from Chondromyces sp. as a potent antitumor agent. Because of its unique chemical structure, a macrolide with a highly unsaturated amide side chain, and potent growth inhibitory effect in various cancer cell lines, Api A is currently in clinical trial for cancer therapy. In the present study, the effect of Api A on in vitro angiogenesis of bovine aortic endothelial cells (BAECS) was investigated. Api A potently inhibited the proliferation of BAECS in a dose-dependent manner. Treatment of the endothelial cells with up to 10 ng/ml of the compound did not show any cytotoxicity. In addition, it inhibited basic fibroblast growth factor (bFGF)-induced invasion and capillary tube formation of BAECS at concentrations of 2-5 ng/ml. These results, therefore, demonstrate that Apl A is a novel antiangiogenic agent and may suppress the growth of tumors, at least in part, by the inhibition of neovascularization.

• Journal of Veterinary Clinics
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• v.21 no.3
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• pp.309-313
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• 2004

The purpose of this study was to determine whether immunosuppresant, rapamycin could inhibit corneal angiogenesis induced by angiogenin and to evalutate the its role by micropocket assay. The rabbit's eye was implanted intrastromally into the superior cornea with pellet for the control group, pellet containing of angiogenin for the angiogenin group, and pellet containing of angiogenin and rapamycin for the rapamycin group. We could observed that the angiogen induced corneal angiogenesis was inhibited by rapamycin. The score of neovascularization was significantly decreased in the rapamycin group than in the angiogenin group at 7 and 10 days after pellet implantation (p < 0.05). Histologically, the cornea treated with rapamycin group also showed much less new vessels than the cornea treated with angiogenin. In conclusion, rapamycin appears to inhibit angiogenin induced angiogenesis in a rabbit corneal micropocket assay and may have therapeutic potential as an antiangiogenic agent.