• Journal of Life Science
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• v.34 no.6
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• pp.399-407
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• 2024

Angiogenesis is the process by which new blood vessels form from existing blood vessels. This phenomenon occurs during growth, healing, and menstrual cycle changes. Angiogenesis is a complex and multifaceted process that is important for the continued growth of primary tumors, metastasis promotion, the support of metastatic tumors, and cancer progression. Impaired angiogenesis can lead to cancer, autoimmune diseases, rheumatoid arthritis, cardiovascular disease, and delayed wound healing. Currently, there are only a handful of effective antiangiogenic drugs. Recent studies have shown that natural marine products exhibit antiangiogenic effects. In a previous study, we reported that the hexane extract of H. fusiformis (HFH) could inhibit the development of new blood vessels both in vitro and in vivo. The aim of this study was to describe the inhibitory effect of chloroform extracts of H. fusiformis on angiogenesis. To investigate how chloroform extract prevents blood vessel growth, we examined its effects on HUVEC, including cell migration, invasion, and tube formation. In a mouse Matrigel plug assay, H. fusiformis chloroform extract (HFC) also inhibited angiogenesis in vivo. Certain proteins associated with blood vessel growth were reduced after HFC treatment. These proteins include vascular endothelial growth factor (VEGF), mitogen-activated protein kinase (MAPK)/extracellular signal transduction kinase, and serine/threonine kinase 1 (AKT). These studies have shown that the chloroform extract of H. fusiformis can inhibit blood vessel growth both in vitro and in vivo.

• Archives of Plastic Surgery
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• v.33 no.1
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• pp.1-4
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• 2006

Cryopreserved fibroblast implants represent a major advancement for healing of chronic wounds. Bone marrow stromal cells, which include the mesenchymal stem cells, have a low immunity-assisted rejection and are capable of expanding profoundly in a culture media. Therefore, they have several advantages over fibroblasts in clinical use. The ultimate goal of this study was to compare the wound healing accelerating growth factor secretion of the bone marrow stromal cells with that of the fibroblasts and this pilot study particularly focuses on the growth factor secretion to accelerate wound healing. Bone marrow stromal cells and fibroblasts were isolated from the same patients and grown in culture. At 1, 3, and 5 days post-incubating, secretion of basic fibroblast growth factor(bFGF), vascular endothelial growth factor (VEGF), and transforming growth factor beta(TGF-${\beta}$) were compared. In TGF-${\beta}$ secretion fibroblasts showed 12~21% superior results than bone marrow stromal cells. In contrast, bFGF levels in the bone marrow stromal cells were 47~89% greater than that in fibroblasts. The VEGF levels of the bone marrow stromal cells was 7~12 fold greater than that of the fibroblasts. Our results suggest that the bone marrow stromal cells have great potential for wound healing accelerating growth factor secretion.

• Journal of Gastric Cancer
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• v.9 no.3
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• pp.96-103
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• 2009

Purpose: Lymph node metastasis is an important factor in determining prognosis and therapeutic options for early gastric cancer (EGC) patients. Vascular endothelial growth factor (VEGF)-C and D are known as lymphangiogenic factors, and cyclooxygenase (COX)-2 is thought to play a role in lymph node metastasis in gastric carcinoma. This study was designed to determine whether the expression of VEGF-C, VEGF-D, and COX-2 is associated with clinicopathologic factors, especially lymph node metastasis in EGCs invading the submucosa. Materials and Methods: Tissue samples were obtained from 85 Patients undergoing standard gastrectomy with lymph node dissection between 1991 and 2007 in the Department of Surgery of Daejeon St. Mary's Hospital in Daejeon, Korea. All patients were diagnosed with gastric cancers and submucosal invasion. We examined the expression of VEGF-C, VEGF-D, and COX-2 using immunohistochemical methods. Results: Of the 85 patients, 16 (18.8%) had lymph node metastasis. VEGF-C, VEGF-D, and COX-2 were positively expressed in 34.1% (29/85), 22.3% (19/85), and 37.6% (32/85) of the patients. VEGF-C and COX-2 expression was significantly correlated with lymph node metastasis (P<0.05). A positive correlation existed between VEGF-C and COX-2 expression (P< 0.001). Conclusion: VEGF-C and COX-2 expression is associated with lymph node metastasis in gastric cancer with submucosal invasion. VEGF-C and COX-2 may thus be predictive markers for lymph node metastasis in EGC patients with submucosal invasion.

• The Korea Journal of Herbology
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• v.30 no.2
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• pp.19-24
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• 2015

Objectives : The experiment was performed to investigate promotive effects of haeae-tang (HET) extract, a traditional Korean medicinal recipe, on hair growth, protein and gene expression in hair-removed C57BL/6. Methods : In experiment, animals were divided into 3 groups including normal (vehicle), HET ethanol extract and 5% minoxidil-treated groups (Minoxidil, positive control). The vehicle or testing samples were daily treated with 0.2ml per on hair-shaved dorsal skin of C57BL/6mice for 15 days. Effects of testing samples on hair growth was monitored through phototrichogram analysis by folliscope on the initial, $5^{th}$, $10^{th}$, $15^{th}$ day, respectively. Also, gene and protein expressions of vascular endothelial growth factor (VEGF) and Insulin like growth factor-1 (IGF-1), relevant to hair growth, were examined. Results : Hair density and hair thickness of Minoxidil treated-group was significantly increased compared to that of vehicle application on the $15^{th}$day, respectively. Dorsal hair density of HET treated-group was significantly increased compared to that of vehicle application on the $15^{th}$day. In addition, the Minoxidil group significantly increased the expression of cutaneous IGF-1 protein and mRNA compared to that of the vehicle-applied group on the $15^{th}$ day. And HET-treated group significantly increased the expression of dorsal VEGF protein compared to that of the vehicle-applied group on the $15^{th}$ day. Conclusions : These results suggest that this Korean medicinal recipe, HET has promoting activity on hair growth in an Alopecia animal model thus it can be used as a material of agent or products for improvement or prevention of alopecia.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.3079-3083
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• 2013

Objective: To investigate the effects of endostar, a recombined humanized endostatin, plus cisplatin on the growth, lymphangiogenesis and lymphatic metastasis of the Lewis lung carcinoma (LLC) in mice. Methods: A tumor model were established in C57BL/6 mice by intravenious transplantation of LLC cells. Then the mice were randomized to receive administration with NS, endostar, cisplatin, or endostar plus cisplatin. After the mice were sacrificed, tumor multiplicity, tumor size and lymph node metastasis were assessed. Then the expression of vascular endothelial growth factor-c (VEGF-C) and podoplanin were determined by immunohistochemical staining. Results: Endostar plus cisplatin significantly suppressed tumor growth. lymphatic metastasis and prolonged survival time of the mice without obvious toxicity. The inhibition of lymphatic metastasis was associated with decreased microlymphatic vessel density (MLVD) and expression of VEGF-C. Conclusions: Endostar combined with cisplatin was more effective to suppress tumor growth and lymphatic metastasis than either agent alone. Thus this may provide a rational alternative for lung carcinoma treatment.

• YAKHAK HOEJI
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• v.60 no.1
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• pp.8-14
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• 2016

Endotoxemia induces production of inflammatory mediators and acute phase proteins, leading to multiorgan injury and systemic inflammation. Hypothalamic-pituitary-adrenal (HPA) axis activation and glucocorticoids (GCs) release modify endotoxemia-induced inflammatory responses. In the present study, we investigated whether pre-exposure of GCs influences endotoxin-induced production of inflammatory mediators in hepatocytes. Hepa1c1c-7 cells were pretreated with low concentrations of corticosterone for 24 h and then cultured without corticosterone in the presence or absence of LPS. Our results demonstrated that LPS alone significantly enhanced production of IL-6 and CRP but reduced vascular endothelial growth factor (VEGF) compared to controls. Combination of corticosterone pretreatment and LPS significantly upregulated production of IL-6, IL-$1{\beta}$, and VEGF but downregulated CRP compared to those in LPS alone. These findings suggest that in low concentration of corticosterone-preexposed hepatocytes, endotoxemia may induce upregulation of IL-6, IL-$1{\beta}$, VEGF and but downregulation of CRP.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.5
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• pp.2081-2086
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• 2015

Gecko is a kind of traditional Chinese medicine with remarkable antineoplastic activity. However, undefined mechanisms and ambiguity regarding active ingredients limit new drug development from gecko. This study was conducted to assess anti-angiogenic properties of the aqueous extracts of fresh gecko (AG) or macromolecular components separated from AG (M-AG). An enzyme-linked immunosorbent assay (ELISA) approach was applied to detect the vascular endothelial growth factor (VEGF) secretion of the tumor cells treated with AG or M-AG. The effect of AG or M-AG on vascular endothelial cell proliferation and migratory ability was analyzed by tetrazolium dye colorimetric method, transwell and wound-healing assays. Chick embryo chorioallantoic membrane (CAM) assays were used to ensure the anti-angiogenic activity of M-AG in vivo. The results showed that AG or M-AG inhibited the VEGF secretion of tumor cells, the relative inhibition rates of AG and M-AG being 27.2% and 53.2% respectively at a concentration of $20{\mu}L/mL$. AG and M-AG inhibited the vascular endothelial (VE) cell proliferation with IC50 values of $11.5{\pm}0.5{\mu}L/mL$ and $12.9{\pm}0.4{\mu}L/mL$ respectively. The VE cell migration potential was inhibited significantly (p<0.01) by the AG (${\geq}24{\mu}L/mL$) or M-AG (${\geq}12\mu}L/mL$) treatment. In vivo, neovascularization of CAM treated with M-AG was inhibited significantly (p<0.05) at a concentration of ${\geq}0.4{\mu}L/mL$. This study provided evidence that anti-angiogenesis is one of the anti-tumor mechanisms of AG and M-AG, with the latter as a promising active component.

• 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.

• Journal of Microbiology and Biotechnology
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• v.12 no.5
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• pp.829-833
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• 2002

Angiogenesis is an essential event in a variety of physiological and pathological processes. Therefore, effective inhibition of this event is a promising strategy for treating angiogenesis-related diseases, including cancer. The current study investigated two unique bafilomycin-type macrolide inhibitors of angiogenesls, PC-766B' (1) and PC-766B (2). The strain RK97-56 which produced the inhibitors was identified as Nocardia sp. by chemotaxonomic analyses, and the purification of the inhibitors was guided by their anti-angiogenic activities. PC-766B' (1) and PC-766B (2) exhibited potent inhibitory activities towards endothelial cell migration stimulated by the vascular endothelial growth factor (VEGF).

• Korean Journal of Acupuncture
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• v.26 no.2
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• pp.27-38
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• 2009

Objectives: Rheumatoid arthritis (RA) is a chronic autoimmune disease, principally characterized by synovial inflammation of the joints. We previously reported the effect of acupuncture for RA, but the mechanism is still unclear. Various factors such as oxidative stress and angiogenesis were involved in the pathogenesis of RA, and recently, it has also been reported that cytokines also play a major role in RA. Thus, we investigated whether acupuncture could induce any changes in the levels of cytokines including vascular endothelial growth factor (VEGF), angiogenin and epidermal growth factor (EGF) as well as erythrocyte sedimentation rate (ESR), c-reactive protein (CRP), and rheumatoid factor (RF) in the sera of RA patients. Methods: The forty three patients who met the American College of Rheumatology (ACR) criteria for RA recruited. The acupuncture group (n=21) underwent 14 sessions of partially individualized acupuncture treatment for 6 weeks, and the control group had no treatment (n=13) over the same periods. We evaluated ESR, CRP and RF. In addition, to find out the mechanism of acupuncture, we assessed the changes of the cytokine activities using protein cytokine array in the sera of the patients. Results: Acupuncture significantly decreased the levels of ESR and CRP, but RF were not changed after 6-week acupuncture treatments. Moreover, acupuncture reduced the levels of VEGF, angiogenin and EGF in the sera of the patients. Interestingly, they were related with angiogenesis, which is an important process in the pathogenesis of RA. The levels of oncostatin, interleukin(IL)-$1{\alpha}$, IL-8, leptin, monocyte chemotactic protein-1, macrophage-derived chemokine, macrophage inflammatory proteins-1, platelet-derived growth factor BB and RANTES were not changed significantly. Conclusions: The effect of acupuncture for reliving RA symptoms can be partially explained by inhibition of angiogenesis factors in the sera of the RA patients.