• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.28 no.6
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• pp.434-439
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• 2002

Oral squamous cell carcinoma (OSCC) is one of the most common head and neck cancers. OSCC generally has a poor prognosis due to its tendency towards a local invasion and subsequent metastasis, which is mediated by multiple proteolytic enzymes and angiogenesis. Soy products contain high levels of isoflavonoids, including the tyrosine kinase inhibitor, genistein, which has been identified as a potent inhibitor of cell proliferation and in vitro angiogenesis. The purpose of this in vitro study is to evaluate the anti-cancer effect of genistein with respect to the angiogenesis and basement membrane invasion in OSCC. The highly invasive OSCC cell line, HSC-3 cells were cultured in the presence of $10{\mu}M$ genistein for 24h. To evaluate the effects of genistein on the invasiveness and the gelatinolytic activity, in vitro invasion assay and zymography were performed. In order to evaluate the effect on the VEGF and bFGF mRNA expression, RT-PCR and northern hybridization reaction, and chemiluminescence detection were applied. The in vitro invasion assay showed that the genistein treatment reduced the cellular invasion through the artificial basement membrane and significant difference between the control group and the genistein treated group was shown in MMP-2 activity. Especially, the 62 kDa activated form of MMP-2 in the control group was 1.8 times higher than that in the genistein treated group. The results of the northern blot analyses indicated that VEGF mRNA expression in the genistein treated group was significantly down regulated. This study showed that genistein inhibits angiogenesis and reduces basement membrane invasion in OSCC. It seems to support the possibility of genistein as an anti-cancer agent.

• THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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• v.7 no.1
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• pp.61-75
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• 2001

The purpose of this study is to prove the angiogenesis effects of WhaYoungJiTongTang (hereinafter referred to as the 'WYJTT'). For the study, by utilizing liver cancer cell line; SK-HEP-1, lung cancer cell line: A549, stomach cancer cell line: AGS and bovine capillary endothelial cell: BCE, the effects of the WYJTT on toxicity and proliferation ability of cells and the effects on anti-angiogenesis of bovine capillary endothelial cell and of mice's aorta were studied. 1. Cell viability assay In comparison with the control group, when $100{\mu}g/ml$ of WYJTT was injected, the viability was reduced in SK-Hep-1, $400{\mu}g/ml$ in A549 and $200{\mu}g/ml$ in AGS. 2. Cell proliferation assay In comparison with the control group, when $600{\mu}g/ml$ of WYITT was injected, DNA synthesis was reduced to 35.1% in the SK-Hep-1, 56.0% in A549, and 25.8% in BCE (bovine capillary endothelial cell); and when $400{\mu}g/ml$ was injected, DNA synthesis was reduced to 12.1 in AGS. 3. Tube formation assay In the event that BCE is injected with WYJTT in each of its content gradient, the anti-angiogenesis was effective in amounts of $400{\mu}g/ml$ with 6 hours of the treatment. 4. Aortic ring assay In comparison with the control group, the angiogenesis was restricted to the remarkable degree in amount of $200{\mu}g/ml$: 10% in $400{\mu}g/ml$; and fully inhibited in each of $800{\mu}g/ml$ and $1600{\mu}g/ml$. As a result of the experiments mentioned above, WYJTT showed its anti-angiogenesis effects against cancer cell line.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.4
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• pp.969-979
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• 2003

Gamisoamsan is a prescription originated in Soamsan which is known as an anti-cancer remedy in the traditional Korean Medicine. To enhance the synergic effects of anti-cancer activity of Soamsan, this study reconstituted the original components of Soamsan with a slight modification and produced a novel herbal remedy, namely Gamisoamsan. To investigate the effects of Gamisoamsan on anti-cancer reaction, I studied the effects of Gamisoamsan on angiogenesis via chorioallantoic membrane (CAM) assay, corneal neovascularization assay and the effects on expression of growth factor which are VEGF, TGF-β, bFGF and IMUP-1. Anti-cancer effects of Gamisoamsan was also abserved through hematological parameters, tumor volume and survival rate in mice. Gamisoamsan inhibited embryonic angiogenesis of blood vessels in CAM assay and inhibited neovascularization of ral cornea. Gamisoamsan reduced cell proliferation in HT1080 cells and IC50 was 2.18 ㎎/㎖ Gamisoamsan reduced the expression of VEGF, TGF-β, bFGF and IMUP-1 which was known as vascular growth factor and this effects of Gamisoamsan was predominant than VP-16. The treatment of Gamisoamsan decreased the CT-26 cell inoculated-tumor volume in mice colon adenocarcinoma and increased mice survival which was inoculated CT-26 cells. The results of the present study suggest that Gamisoamsan extracts has a potential anti-tumor activity and may be an useful remedy to prevent and/or treat cancer.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.19 no.3 s.31
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• pp.22-33
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• 2006

Objective : Angiogenesis induced by hypoxia and inflammation are an essential process of solid tumors and psoriasis. We researched the HIF-1 ${\alpha}$ (hypoxia inducible factor 1 alpha), VEGF(Vascular Endothelial Growth Factor), survival related PI3K-Akt, and inflammation related COX-2 protein expressions to get the information of the mechanism and effects of Rehmannia glutinosa in HepG2 and HaCaT cell lines. Method : To investigate the roles of the Rehmannia glutinosa extract, we performed MTS assay and western blots using HaCaT cells and HepG2 cells. HaCaT cells and HepG2 cells were treated with $50{\mu}g/ml$ and $100{\mu}g/ml$ Rehmannia glutinosa extracts. After 4hrs, HaCaT cells were treated with IGF-II protein for 24hrs and HepG2 cells were treated with $CoCl_2$. Results : 1. We could ohserve that the reduction of the protein level of HIT-1 ${\alpha}$ induced by IGF-II in HaCaT cells. 2. We Could ohserve that the decreased PI3K-Akt and COX-2 expression level by Rehmannia glutinosa extracts treated in HaCaT cells independently ith ERK1/2. 3. We could observe that the reduction of the protein level of HIF-1 ${\alpha}$ induced by $CoCl_2$ in HepG2 cells. Conclusion : These results suggest that Rehmannia glutinosa extracts contributes to the anti-survival pathway and anti-inflammatory activities. Also, we could assume that Rehmannia glutinosa act as anti-inflanmmatory or anti-hypoxia agents via reduction of COX-2 and HIF-1 ${\alpha}$.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.2
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• pp.737-741
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• 2014

Background: In recent years a wide variety of flavonoids or polyphenolic substances have been reported to possess substantial anti-carcinogenic and antimutagenic activities. Grape proanthocyanidins (GPC) are considered as good examples for which there is evidence of potential roles as anti-carcinogenic agents. Methods: A xenograft model was established using H22 cells subcutaneously injected into mice and used to assess different concentrations of grape proanthocyanidins (GPC) and Endostar. Treatments were maintained for 10 days, then levels of vascular endothelial growth factor (VEGF) and microvessel density (MVD) were examined by immunohistochemistry, while VEGF mRNA was determined by real-time PCR in tumor tissue. Results: The expression of MVD and VEGF decreased gradually as the concentration of GPC increased.There was a significant positive correlation between MVD and VEGF. Conclusions: These results suggest that GPC restrains the growth of tumor, possibly by inhibiting tumour angiogenesis.

• Bulletin of the Korean Chemical Society
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• v.32 no.8
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• pp.2823-2826
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• 2011

• The Journal of Korean Medicine
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• v.22 no.2
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• pp.22-30
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• 2001

This study was attempted to investigate the anti-tumor and anti-metastatic effects of Sobokchukeotang(SBCT) and Kamisobokchukeotang(KSBCT). Cytotoxicity against various cancer cell lines, anti-adhesion, pulmonary colonization, anti-angiogenesis, and T/C% were evaluated. SBCT and KSBCT exhibited no cytotoxicity against HT-1080, A549, SK-OV-3, B16-F10 and SK-Mel-2 cell lines. In inhibitory effect on DNA topoisomerase I, the $IC_{50S}$ were shown $250-500{\;}\mu\textrm{g}/ml$ of SBCT and $62.5-125{\;}\mu\textrm{g}/ml$ of KSBCT respectively. In the in vivo experiments, SBCT(135.98%) and KSBCT(151.92%) apparently increased the life span of mice bearing sarcoma-180. KSBCT significantly inhibited the adhesion of HT-1080 to complex extracellular matrix in a dose-dependent manner in contrast to SBCT. In pulmonary colonization assay by B16-F10, a number of colonies in the lungs were decreased more significantly in KSBCT group than those in SBCT group. In vitro neovascularization and CAM assay, angiogenesis was more significantly inhibited in KSBCT-treated group than in SBCT- treated group. Above results suggests that KSBCT is more effectively applied to prevention and treatment of cancer than SBCT.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.20
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• pp.9039-9043
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• 2014

There is a continuing need for innovative alternative therapies for liver cancer. DNA vaccines for hormone/growth factor immune deprivation represent a feasible and attractive approach for cancer treatment. We reported a preventive effect of a DNA vaccine based on six copies of the B cell epitope GRP18-27 with optimized adjuvants against H22 hepatocarcinoma. Vaccination with pCR3.1-VS-HSP65-TP-GRP6-M2 (vaccine) elicited much higher level of anti-GRP antibodies and proved efficacious in preventing growth of transplanted hepatocarcinoma cells. The tumor size and weight were significantly lower (p<0.05) in the vaccine subgroup than in the control pCR3.1-VS-TP-HSP65-TP-GRP6, pCR3.1-VS-TP-HSP65-TP-M2 or saline subgroups. In addition, significant reduction of tumor-induced angiogenesis associated with intradermal tumors of H22 cells was observed. These potent effects may open ways towards the development of new immunotherapeutic approaches in the treatment of liver cancer.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.3
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• pp.557-562
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• 2006

Hypoxia induced angiogenesis and inflammation are essential processes for metastasis and progress of solid tumors. We examined the anti-angiogenic and inflammation related activity of Kochiae Fructus (KF) extract. To investigate the roles of the KF extract, we performed MTS assay, western blots using HaCaT cells and $HepG_2$ cells. The results are as follows. The protein level of $HIF-1{\alpha}$ was reduced when induced by $CoCl_2$ in $HepG_2$ cells treated with KF extract and induced by IGF-11 in HaCaT cells treated with KF extract. KF extract reduced the mRNA level of VEGF in HaCaT cells and KF extract reduced the protein level of iNOS in HaCaT cells. These results suggest that KF extract contributes to the anti-angiogenic and anti-inflammatory activities and also we could assume that KF extract act as antioxidant or anti-inflammatory agents via reduction of $HIF-1{\alpha}$.

• Molecules and Cells
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• v.21 no.2
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• pp.213-217
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• 2006

Although AIMP1 (previously known as p43) is one of three auxiliary proteins bound to a macromolecular aminoacyl tRNA complex, it is also secreted as a cytokine controlling both angiogenesis and immune responses. Here we show that systemically administered purified recombinant human AIMP1 had anti-tumor activity in mouse xenograft models. In Meth A-bearing Balb/c mice, tumor volume increased about 28 fold in the vehicle treatment group, while an increase of about 16.7 fold was observed in the AIMP1-treated group. We also evaluated the anti-tumor activity of AIMP1 in combination with a sub-clinical dose of the cytotoxic anti-tumor drug, paclitaxel. The growth of NUGC-3 human stomach cancer cells was suppressed by 84% and 94% by the combinations of 5 mg/kg paclitaxel + 25 mg/kg AIMP1 (p = 0.03), and 5 mg/kg paclitaxel + 50 mg/kg AIMP1 (p = 0.02), respectively, while 5 mg/kg paclitaxel alone suppressed growth by only 54% (p = 0.02). A similar cooperative effect of AIMP1 and paclitaxel was observed in a lung cancer xenograft model. These results suggest that AIMP1 may be useful as a novel anti-tumor agent.