• Tuberculosis and Respiratory Diseases
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• 제64권3호
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• pp.200-205
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• 2008

연구배경: 혈관신생은 종양의 성장과 유지 및 전이에 필수적이며 따라서 종양조직은 혈관신생을 위해 많은 종류의 혈관형성 촉진인자들을 생성하고 있다. VEGF와 bFGF는 혈관신생과 관련되는 물질로 본 연구에서는 폐암환자에서 조직 내 VEGF와 bFGF의 발현에 대해 알아보고자 하였다. 방법: 조직학적으로 샘암종 또는 편평상피세포암종으로 진단받고 완치의 목적으로 수술을 시행 받은 35명의 폐암환자 조직에서 VEGF 및 bFGF의 농도를 ELISA 방법으로 측정하였으며 이에 대한 임상적 양상을 후향적으로 분석하였다. 결과: VEGF 및 bFGF의 농도는 종양조직이 대조조직보다 유의하게 높았으며 T2+T3의 종양조직이 T1의 종양 조직보다 유의하게 VEGF의 농도가 높았다. 림프절 전이가 있었던 경우가 없었던 경우보다 종양조직에서 VEGF의 농도가 증가한 경향을 보였다(p=0.06). 하지만 VEGF 및 bFGF의 농도는 환자의 병기 및 생존율에 통계적으로 유의한 차이를 보이지 않았다. 결론: VEGF 및 bFGF 모두 종양조직에서 증가하였으나 VEGF만이 종양크기, 림프절 전이 등의 임상양상과 연관성을 보여주었다. 하지만 각각의 VEGF 및 bFGF의 종양조직 내 농도는 예후와 관련되지는 않았다.

• IMMUNE NETWORK
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• 제3권1호
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• pp.38-46
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• 2003

Background: Platelet-activating factor (PAF) induces nuclear factor $(NF)-{\kappa}B$ activation and angiogenesis and increases tumor growth and pulmonary tumor metastasis in vivo. The role of $NF-{\kappa}B$ activation in PAF-induced angiogenesis in a mouse model of Matrigel implantation, and in PAF-mediated pulmonary tumor metastasis were investigated. Methods: Angiogenesis using Matrigel and experimental pulmonary tumor metastasis were tested in a mouse model. Electrophoretic mobility shift assay was done for the assessment of $NF-{\kappa}B$ translocation to the nucleus. Expression of angiogenic factors, such as tumor necrosis factor $(TNF)-{\alpha}$, interleukin $(IL)-1{\alpha}$, basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) were tested by RT-PCR and ELISA. Results: PAF induced a dose- and time-dependent angiogenic response. PAF-induced angiogenesis was significantly blocked by PAF antagonist, CV6209, and inhibitors of $NF-{\kappa}B$ expression or action, including antisense oligonucleotides to p65 subunit of $NF-{\kappa}B$ (p65 AS) and antioxidants such as ${\alpha}$-tocopherol and N-acetyl-L-cysteine. In vitro, PAF activated the transcription factor, $NF-{\kappa}B$ and induced mRNA expression of $TNF-{\alpha}$, $IL-1{\alpha}$, bFGF, VEGF, and its receptor, KDR. The PAF-induced expression of the above mentioned factors was inhibited by p65 AS or antioxidants. Also, protein synthesis of VEGF was increased by PAF and inhibited by p65 AS or antioxidants. The angiogenic effect of PAF was blocked when anti-VEGF antibodies was treated or antibodies against $TNF-{\alpha}$, $IL-1{\alpha}$, and bFGF was co-administrated, but not by antibodies against $TNF-{\alpha}$, $IL-1{\alpha}$, and bFGF each alone. PAF-augmented pulmonary tumor metastasis was inhibited by p65 AS or antioxidants. Conclusion: These data indicate that PAF increases angiogenesis and pulmonary tumor metastasis through $NF-{\kappa}B$ activation and expression of $NF-{\kappa}B$-dependent angiogenic factors.

• 한국임상수의학회지
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• 제18권4호
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• pp.324-328
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• 2001

This study was performed to evaluate the effects of $AS_2O_3$ upon antiangiogenesis in rat cornea, to examine it\`s possible application as an anticancer drug and to provide basic data for further studies of antiangiogenetic mechanism of $AS_2O_3$ . Angiogenesis was induced by cornea micropocket assay, as previously described. Sixteen of forty-eight eyes of Sprague-Dawley rats were randomly assigned to one of three groups, namely, only a bFGF group(control group), and a group treated by $AS_2O_3$ ($AS_2O_3$ group). After pellet implantation, we measured the number of new vessels, vessel length and clock hour of neovascularization, and area of neovascularization was determined using a mathematical formula. New vessels growing began at day 3, number of vessels in $AS_2O_3$ group were significantly more less than those in control group (p<0.05). The length of vessels of $AS_2O_3$ group was significantly shorter than that of control group after day 3(p<0.05). The clock hours of all group were slowly increased at all days but $AS_2O_3$ group was inhibited more than control group. Neovascularization areas of $AS_2O_3$ group were more significantly inhibited than those of control group (p<0.05). This study showed that $AS_2O_3$ had powerful antiangiogenetic effects and it would be useful in the choice of anticancer drug.

• Biotechnology and Bioprocess Engineering:BBE
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• 제5권2호
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• pp.106-109
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• 2000

Vascular endothelial cells (EGs) are usually difficult to culture to culture in a large scale because of their complicated requirements for cell growth. As the vascular endothelial growth factor (VEGF) is a key growth factor in the EC culture, we transfected human umbilical vein endothelial cells (HUVEC) using a plasmid containing VEGF gene and let them grow in a culture medium eliminated an important supplement, endothelail cell growth supplement(ECGS). The expression of VEGF by HUVEC tansfected with Vegf GENE was not enough to stimulate the growth of HUVEC, only 40% of maximum cell density obtainable in the presence of ECGS. However, when the culture medium was supplied with 2.5 ng/ml of basic fibroblast growth factor (bFGF), a synergistic effect effect of VEGE and bFGF was observed. In this case, the final cell density was recovered was recovered up to about 78% of maxium value.

• 생명과학회지
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• 제14권3호
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• pp.375-384
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• 2004

FGFs는 Xenopus의 초기 배발생에서 중배엽 형성, 전후축패턴형성, scatter factor로서 낭배기의 기관형성에 관여하는 등 다양한 기능을 가지고 있는 것으로 알려져 있다 그 중 bFGF는 배양 분리편으로부터 다양한 기관을 유도해낼 수 있으며 그 효과는 처리시간 및 농도 의존적이라고 알려져 왔다. 본 연구는 Xenopus의 예정표피역을 분리하여 bFGF와 HGF을 단독 및 복합처리 하였을 때 기관분화 및 유도효과를 검토하기 위하여 실시하였다. 단독처리 및 복합 처리된 배양액에 동물극 분리편을 정상배가 st. 43에 이를 때까지 2$0^{\circ}C$에서 3일간 배양하여 조직학적 및 면역조직화학적 방법으로 조직의 분화양상을 확인하였다. 성장인자는 bFGF를 0, 0.5, 1. 10. 50 ng/ml의 농도와 HGF를 0, 1, 10, 50, 100ng/ml의 농도로 조합하여 처리한 결과 bFGF 단독처리 때보다 HGF와의 혼합처리에서 기관분화율의 상승효과가 관찰되었다. 분화된 기관은 1 ng/ml의 bFGF 와 10ng/ml의 HGF, 10ng/ml의 bFGF와 1ng/ml의 HGF의 농도에서 매우 다양한 것으로 나타났다. 눈은 1과 10ng/ml의 bFGF ,그리고 1과 10 ng/ml의 HGF 농도조합에서 높은 비율로 분화하였다. 또한 분리편 배양에 의해 유도된 눈과 정상 배의 눈에서 RPE65를 인식하는 단일클론 항체 40All, 25F5를 사용하여 AP 반응이 강하게 나타나 눈의 유도를 확인할 수 있었다.

• Journal of Korean Neurosurgical Society
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• 제29권12호
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• pp.1584-1591
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• 2000

Objective : Until now, it has been little known about the biological mechanisms associated with the genesis, growth, and rupture of intracranial aneurysm. This study was performed to investigate and understand a part of these mechanisms. Materials and Methods : Immunohistochemical stains for angiogenesis growth factors(basic fibroblast growth factor (bFGF) and vascular endothelial growth factor(VEGF)) and selected vascular wall matrix proteins(alpha smooth muscle actin(${\alpha}SMA$) and collagen Type IV) were performed in fixed sections from a normal circle of Willis artery which was taken from the autopsy specimen as a control vessel and 17 aneurysmal wall specimens which was taken during surgical clipping of aneurysms. The staining intensity and distribution of immunoreactivity to angiogenesis growth factors and selected wall matrix proteins in control vessel and aneurysmal wall were examined and compared with each other. The difference of staining intensity according to the size of aneurysm was also investigated. Results : There was no immunoreactivity to bFGF and VEGF in the control vessel. bFGF immunoreactivity was exhibited in 15 of 17 aneurysm specimens around smooth muscle cells within the media of aneurysm. VEGF immunoreactivity was also exhibited in all aneurysm specimens in patches or diffusely affecting all layers of the aneurysmal wall. The degrees of intensity of bFGF and VEGF immunoexpression were proportionate roughly to the size of aneurysm. Strong immunoexpression of both factors were noticed in large aneurysm. A regularly arranged and defined band of immunoreactivity of ${\alpha}SMA$ was noticed in the media of the control vessel, whereas diffuse, faint, irregularly arranged ${\alpha}SMA$ was noticed in the aneurysmal wall. A regularly defined band of collagen Type IV immunoreactivity was also noticed in the subendothelium of the control vessel, whereas diffuse disorganized immunoreactivity of collagen Type IV was noticed in the entire wall of the aneurysm. Conclusion : These results indicate substantial evidences of abnormal expression of angiogenesis factors and changes of selected vascular wall matrix proteins in the wall of intracranial aneurysm. The unbalanced changes of angiogenesis factors and vascular wall matrix proteins in the wall of aneurysm may be one of the biological mechanisms for the growth and rupture of aneurysm.

• 한국약용작물학회지
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• 제15권5호
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• pp.311-314
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• 2007

Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are the most important angiogenic molecules associated with tumor-induced neovascularization. This study was carried out to investigate inhibitory effect of extracts from root of Rehmannia glutinosa LIBOSCHITZ (Rehmannia Radix and Rehmannia Radix Preparata) on endothelial cell proliferation. The methanol extracts from the medicinal herb were fractionated into n-hexane, ethyl acetate, n-butanol and aqueous fractions. Among the four fractions, the n-butanol fraction from R. Radix on exhibited highly effective inhibition (${\approx}79%$ inhibition) on the binding of KDR/Flk-1-Fc to immobilized $VEGF_{165}$ and then ethyl acetate fraction from R. Radix (${\approx}45%$ inhibition) at the concentration of $100\;{\mu}g/ml$. The n-butanol fraction efficiently blocked the VEGF- and bFGF-induced HUVEC proliferation in a dose-dependent manner, but did not affect the growth of HT1080 human fibrosarcoma cells. The n-butanol fraction more efficiently blocked the binding of KDR/Flk-1-Fc to immobilized $VEGF_{165}$ and VEGF- and bFGF-induced human umbilical vein endothelial cell proliferation than the fraction from R. Radix Preparata. Our results suggest that Rehmannia Radix may be used as a candidate for developing anti-angiogenic agent.

• 대한한의학회지
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• 제26권4호
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• pp.22-30
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• 2005

Objectives: Recently, angiogenesis has gained an increasing interest as a prognostic factor in breast cancer. In this study we aimed to assess the anti angiogenic effects of HAD, a botanical anticancer remedy which has been prescribed in Daejeon University Oriental Hospital in Korea, on patients with breast carcinoma by measuring the serum vascular endothelial growth factor (VEGF), basic fibroblast growth factor (b-FGF) and platelets levels. Methods: The study included 26 consecutive breast cancer patients (mean age$\pm$standard deviation: 47.5$\pm$8.7 years) with stage II to IV disease who were treated with HAD (mean duration $\pm$ standard deviation: 264.5$\pm$121.6 days). In addition to routine laboratory and staging procedures, serum VEGF, b-FGF levels and platelet counts were determined as antiangiogenic markers. The antiangiogenic effects of HAD were evaluated by analyzing the differences between the values of the antiangiogenic markers before and after the treatment with HAD. Results: Serum b-FGF concentrations were significantly reduced after the treatment with HAD (P=0.042). Serum VEGF concentrations were found to have a somewhat decreasing change, though the change was not statistically significant (P=0.229). Platelet counts had little changes (P=O.80). Conclusions: It is supposed that HAD has effects on decreasing the serum b-FGF levels related with the clinical outcome of breast cancer patients.

• Applied Microscopy
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• 제43권1호
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• pp.27-33
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• 2013

Inflammatory cells express the inflammatory cytokines and growth factors induced by lipopolysaccharide (LPS). Odontoblasts are located at the pulp-dentin interface and extend their cell processes far into the dentin where they are the first cells to encounter microorganisms or their products. Therefore, this study examined the expression of some growth factors related to the signal pathway, such as growth factor receptor binding protein 2 (Grb2)-Ras in odontoblast-like dental pulp cells, after a treatment with LPS. After 60 minutes, the mRNA and protein expression levels of Grb2 and Ras were higher in the LPS-treated cells than in the control cells. The level of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) mRNA expression was increased significantly to a level similar to that of Grb2 and Ras at 60 minutes. The platelet-derived growth factor-AA (PDGF-AA) mRNA level was expressed strongly in the odontoblast like dental pulp cells without an association with LPS stimulation. Scanning electron microscopy revealed many extensions of the cytoplasmic processes and the number of processes increased gradually at 30, 60 and 90 minutes after LPS stimulation. From these results VEGF and bFGF expression might be induced through the Grb2-Ras signal transduction pathway in LPS treated odontoblasts.

• Archives of Plastic Surgery
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• 제33권1호
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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.