• 생명과학회지
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• 제26권1호
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• pp.59-67
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• 2016

도라지는 다양한 종류의 triterpenoid계통의 saponin을 함유한 다년생 식물이다. 도라지는 한국에서 오랫동안 식품으로 사용되어 왔으며 그 추출물에 관한 생리활성연구도 많이 보고되었으나, 발효 도라지추출물에 관한 혈관기능 연구는 미미한 실정이다. 본 연구자들은 먼저 도라지 추출물을 발효시킨 후, 발효도라지추출물을 제조하였으며, 제조된 발효도라지추출물이 혈관내피세포에 어떤 효과를 미치는 지 관찰하였다. BAEC에 발효도라지추출물을 농도 별로 처리하였을 때, 고농도(100 μg/ml)에서는 혈관내피세포의 탈착이 일어났으며, 저농도(0.1 μg/ml)에서는 세포탈착은 일어나지 않았으나 세포성장과 세포이동이 촉발됨을 관찰하였다. 고농도에서 일어난 세포탈착은 세포사 즉, 세포사멸, 세포괴사, 오토파지 등과는 관련이 없었다. 또한 고농도의 도라지 추출물은 혈관내피세포에서 유래한 작은 vesicle을 형성하였는데, 이 vesicle은 세포사멸과 관련이 없기 때문에 내피세포에서 유래된 EMP로 추측된다. 흥미롭게도 고농도의 세포탈착 현상은 EMP로 추측되는 vesicle에 의하여 일어난 현상이었다. 저농도의 도라지 추출물이 유발한 세포이동과 세포성장은 혈관내피세포의 중요한 신호전달물질중의 하나인 Akt의 활성화를 통해 일어남을 확인하였다. 결론적으로 도라지 추출물은 혈관내피세포의 성장을 촉진함으로써 혈관의 안정성을 유지하고 세포성장과 이동을 촉발함으로써 상처치유에 효과를 나타낼 수 있음을 본 연구를 통하여 확인하였다.

• Asian Pacific Journal of Cancer Prevention
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• 제14권6호
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• pp.3851-3854
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• 2013

Objective: To explore changes in the serum tumor makers, hypoxia-inducible factor-$1{\alpha}$ (HIF-$1{\alpha}$) and vascular endothelial growth factor (VEGF) level and their relations in patients with non-small cell lung cancer (NSCLC) before and after intervention. Materials and Methods: Forty patients with NSCLC and 40 healthy individuals undergoing physical examination in our hospital provided the observation and control groups. HIF-$1{\alpha}$ and VEGF levels in serum were detected by enzyme-linked immuno-sorbent assay (ELISA) in the observation group before and after intervention and in control group on the day of physical examination, along with serum carcino-embryonic antigen (CEA), neuron-speci ic enolase (NSE) and squamous cell carcinoma antigen (SCC) levels in the observation group with a fully automatic biochemical analyzer. Clinical effects and improvement of life quality in the observation group were also evaluated. Results: The total effective rate and improvement of life quality after treatment in observation group were 30.0% and 32.5%, respectively. Serum HIF-$1{\alpha}$ and VEGF levels in the control group were lower than that in observation group (p<0.01), but remarkably elevatedafter intervention (p<0.01). In addition, serum CEA, NSE and SCC levels were apparently lowered by treatment (p<0.01). Serum HIF-$1{\alpha}$ demonstrated a positive relation with VEGF level (p<0.01) and was inversely related with CEA, NSE and SCC levels (p<0.01). Conclusions: Significant correlations exist between marked increase of serum HIF-$1{\alpha}$ and VEGF levels and decrease of indexes related to hematological tumor markers in NSCLC patients after intervention.

• IMMUNE NETWORK
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• 제11권6호
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• pp.368-375
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• 2011

Background: Recent clinical observation reported that there was a significant correlation between change in circulating vascular endothelial growth factor (VEGF) levels and the occurrence of severe acute graft-versus-host disease (GVHD) following allogeneic hematopoietic stem cell transplantation (allo-HSCT), but the action mechanisms of VEGF in GVHD have not been demonstrated. Methods: This study investigated whether or not blockade of VEGF has an effect on acute GVHD in a lethally irradiated murine allo-HSCT model of $B6\;(H-2^b)\;{\rightarrow}B6D2F1\;(H-2^{b/d})$. Syngeneic or allogeneic recipient mice were injected subcutaneously with anti-VEGF peptides, dRK6 ($50{\mu}g/dose$) or control diluent every other day for 2 weeks (total 7 doses). Results: Administration of the dRK6 peptide after allo-HSCT significantly reduced survival with greaterclinical GVHD scores and body weight loss. Allogeneic recipients injected with the dRK6 peptide exhibited significantly increased circulating levels of VEGF and expansion of donor $CD3^+$ T cells on day +7 compared to control treated animals. The donor $CD4^+$ and $CD8^+$ T-cell subsets have differential expansion caused by the dRK6 injection. The circulating VEGF levels were reduced on day +14 regardless of blockade of VEGF. Conclusion: Together these findings demonstrate that the allo-reactive responses after allo-HSCT are exaggerated by the blockade of VEGF. VEGF seems to be consumed during the progression of acute GVHD in this murine allo-HSCT model.

• 대한수의학회지
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• 제28권1호
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• pp.137-143
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• 1988

국내(國內)에서 분리(分離)된 porcine enterovirus(serotype 3)를 초유(初乳)를 섭취(攝取)하지 않은 자돈(仔豚)에 경구감염(經口感染) 시킨 후 회백뇌척수염(灰白腦脊髓炎)을 나타내는 시기(時期)에 중추신경계(中樞神經系) 혈관내피세포(血管內皮細胞)를 전자현미경적(電子顯微鏡的)으로 관찰(觀察)하였던 바 다음과 같은 결과(結果)를 얻었다. 척수(脊髓) 및 소뇌(小腦) 혈관내피세포(血管內皮細胞)에서는 picornavirus의 특징적(特徵的)인 virus결정체(結晶體)가 출현(出現)하였고 virus결정체(結晶體)는 rough ER과 밀접하게 연결되어 있었으며 수막(髓膜)의 혈관내피세포(血管內皮細胞)에서도 전자밀도(電子密度)가 높은 virus양(樣) 입자(粒子)들의 응집체(凝集體)가 관찰(觀察)되었다. 세포소기관(細胞小器官)의 변화(變化)로는 mitochondria의 확장(擴張)과 cristae의 소실(消失), rough ER의 확장(擴張)과 ribosome의 탈락(脫落)이 현저하였다. 또한 혈관주위강(血管周圍腔)의 확장(擴張)과 임파구(淋巴球)의 침윤(浸潤), 현관내피세포(血管內皮細胞)의 세포막(細胞膜)과 기저막(基底膜)의 파괴(破壞)가 인정(認定)되었다.

• BMB Reports
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• 제51권2호
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• pp.79-84
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• 2018

Niemann-Pick type C disease (NP-C) is a fatal neurodegenerative disorder caused by a deficiency of NPC1 gene function, which leads to severe neuroinflammation such as astrogliosis. While reports demonstrating neuroinflammation are prevalent in NP-C, information about the onset and progression of cerebellar astrogliosis in this disorder is lacking. Using gene targeting, we generated vascular endothelial growth factor (VEGF) conditional null mutant mice. Deletion of VEGF in cerebellar Purkinje neurons (PNs) led to a significant increase of astrogliosis in the brain of NP-C mice in addition to the loss of PNs, suggesting PN-derived VEGF as an important factor in NP-C pathology. Moreover, replenishment of VEGF in neurons improved brain pathology in NP-C mice. Overall, our data provide a new pathological perspective on cerebellar astrogliosis in NP-C and suggest the importance of VEGF as a therapeutic target for this disease.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제31권1호
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• pp.27-34
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• 2009

Angiogenesis is essential for solid tumor growth and progression. Among the pro-angiogenetic factors, vascular endothelial growth factor(VEGF), also known as vascular permeability factor, is the most important as a mitogen for vascular endothelium. The VEGF family of molecules currently consists of six growth factors, VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-E, and placenta growth factor(PlGF). Over-expression of PlGF is associated with angiogenesis under pathological conditions such as ischemia, inflammation, and cancer. Hence, the goal of this study is to identify the correlation of clinicopathlogical factors and the up-regulation of PlGF expression in oral squamous cell carcinoma. We studied the immunohistochemical staining of PlGF, PlGF gene expression and a real time quantitative RT-PCR in 20 specimens of 20 patients with oral squamous cell carcinoma. The results were as follows. 1. In the immunohistochemical study of poorly differentiated and invasive oral squamous cell carcinoma, the high level staining of PlGF was observed. And the correlation between immunohistopathological PlGF expression and histological differentiation of specimens was significant (Pearson correlation analysis, significance [r] >0.6, P < .05). 2. In the PlGF gene RT-PCR analysis, PlGF expression was more in tumor tissue than in adjacent normal tissue. Paired-samples analysis determined the difference of PlGF mRNA expression level between the cancer tissue and the normal tissue (Student's t - test, P < .05) These findings suggest that up-regulation of the PlGF gene may play a role in progression and local metastasis in invasive oral squamous cell carcinoma.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제34권4호
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• pp.239-245
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• 2012

Purpose: Vascular endothelial growth factor (VEGF) plays a key role in tumor angiogenesis and lymphangiogenesis including induction of endothelial cell proliferation, migration and capillary tube formation. E7080 (S1164, Selleck chemical, Houston, TX, USA) is a muti-targeted kinase inhibitor, which targets VEGF receptor-2, 3 (VEGFR-2, 3) and inhibits survival and proliferation of tumor cell. The purpose of this study was to determine the anti-tumor effect of E7080 on oral squamous cell carcinoma. Methods: An oral squamous cell carcinoma cell line, SCC-9 was used in this study. E7080 was applied to SCC-9 cells by 3 different concentrations (1, 5, 10 ${\mu}g/mL$). Control means no application of E7080. The cellular growth was evaluated by real-time cell electronic sensing and MTT assay. The signal transduction was evaluated by Western blotting. Results: In experimental group, SCC-9 cell proliferation was decreased and the VEGFR-3 downstream pathways were inhibited compared with control. Furthermore, increasing the concentration of E7080, the ability of E7080 to disturbance of SCC-9 cell proliferation was increased. Conclusion: Proliferation of SCC-9 cells was inhibited by E7080, which was through by inhibition of VEGFR-3 downstream pathway. In vivo study with E7080 will be required to provide therapeutic benefits in oral squamous cell carcinoma.

• 대한의용생체공학회:의공학회지
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• 제17권3호
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• pp.355-364
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• 1996

Construction of the stable monolayer of endothelial cells onto physicochemically modified polymeric surFace is one of the appropriate method to develop the small caliber vascular graft with the long-term patency. In this study, we constructed the monolayer of endothelial cells on the fibronectin rind the extracellular matrix-coated polyurethane surface derived from human fibroblast cells. To elucidate the adhesion strength of endothelial cells on the extracellular matrix-coated polyurethane, a laminar flow chamber apparatus was developed to exposure the shear stress on the apical membrane of ondothelial cells. Endothelial cells show the strongest adhesion after two days of seeding onto the fibronectin-coated polyurethane surface, whereas endothelial cells on the extracellular matrix derived from the human flbroblast cells show the minimal doubling time of cellular growth.

• The Korean Journal of Physiology and Pharmacology
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• 제20권5호
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• pp.533-538
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• 2016

Angiogenesis plays an essential role in embryo development, tissue repair, inflammatory diseases, and tumor growth. In the present study, we showed that endothelial nitric oxide synthase (eNOS) regulates retinal angiogenesis. Mice that lack eNOS showed growth retardation, and retinal vessel development was significantly delayed. In addition, the number of tip cells and filopodia length were significantly reduced in mice lacking eNOS. Retinal endothelial cell proliferation was significantly blocked in mice lacking eNOS, and EMG-2-induced endothelial cell sprouting was significantly reduced in aortic vessels isolated from eNOS-deficient mice. Finally, pericyte recruitment to endothelial cells and vascular smooth muscle cell coverage to blood vessels were attenuated in mice lacking eNOS. Taken together, we suggest that the endothelial cell function and blood vessel maturation are regulated by eNOS during retinal angiogenesis.

• 환경생물
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• 제27권1호
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• pp.88-94
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• 2009

안토시아닌(Anthocyanin)은 플라보노이드계 화합물의 한 부류로 항산화, 항암 및 항궤양, 항당뇨, 중금속해독, 시력보호, 콜레스테를 저하 등의 다양한 생리활성을 가지는 것으로 보고되어 있다. 죽상경화과정은 염증성 사이토카인의 분비 또는 혈관손상으로 인한 백혈구의 부착과 이동을 통해 시작된다. 본 연구는 이러한 죽상경화의 초기과정에서 안토시아닌 혼합물 중 single compound인 delphinidin chloride (DC) 인간혈관 내피세포주(HUVEC, human umbilical vein endothelial cell line)에서 백혈구 부착과 관련이 있는 ICAM-1 (Intraceliular Adhesion Molecule-1)과 VCAM-1 (Vascular Adhesion Molecule-1) 발현에 미치는 영향에 대해 조사하였다. 세포독성이 없는 농도에서 TNF-$\alpha$에 의해 유도된 혈관 내피세포에 대한 단핵구의 부착정도를 측정하기 위해 monocyte-endothelial cell adhesion assay와 광학현미경을 이용한 형태학적 관찰을 한 결과 DC가 처리농도 의존적으로 부착을 억제하였다. 내피세포로부터 TNF-$\alpha$에 의해 유도된 세포부착 분자인 VCAM-1과 ICAM-1의 발현에 대한 영향을 western blot analysis 및 RT-PCR방법으로 비교 분석한 결과 VCAM-1과 ICAM-1의 단백질과 mRNA수준에서의 발현이 농도 의존적으로 감소되었다. 이러한 결과들을 종합해 볼 때 안토시아닌 중에서 DC를 실험한 결과 DE는 TNF-$\alpha$에 의해 유도된 내피세포의 ICAM-1과 VCAM-1 발현 억제효과를 확인할 수 있었다.