• BMB Reports
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• 제42권11호
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• pp.737-742
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• 2009

Hypoxia-inducible factor-$1{\alpha}/{\beta}$ (HIF-$1{\alpha}/{\beta}$) is a heterodimeric transcriptional activator that mediates gene expression in response to hypoxia. HIF-$1{\alpha}$ has been noted as an effective therapeutic target for ischemic diseases such as myocardiac infarction, stroke and cancer. By using a yeast two-hybrid system and a random peptide library, we found a 16-mer peptide named F29 that directly interacts with the bHLH-PAS domain of HIF-$1{\alpha}$. We found that F29 facilitates the interaction of the HIF-$1{\alpha/\beta}$ heterodimer with its target DNA sequence, hypoxia-responsive element (HRE). The transient transfection of an F29-expressing plasmid increases the expression of both an HRE-driven luciferase gene and the endogenous HIF-1 target gene, vascular endothelial growth factor (VEGF). Taken together, we conclude that F29 increases the DNA-binding ability of HIF-$1{\alpha}$, leading to increased expression of its target gene VEGF. Our results suggest that F29 can be a lead compound that directly targets HIF-$1{\alpha}$ and increases its activity.

• Applied Microscopy
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• 제39권2호
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• pp.81-87
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• 2009

당뇨병성 망막증의 당뇨병 합병증의 주요한 증상중의 하나로 망막의 구조적 기능적 변화를 초래한다. 레닌-안지오텐신 시스템은 당뇨병성 망막증의 발병에 주요한 역할을 담당하며 angiotensin I을 angiotensin II로 전환하는 데 담당하는 안지오텐신 전환 효소 (ACE)는 레닌-안지오텐신 시스템의 주요한 요소이다. VEGF는 실명을 일으키는 당뇨병성 망막증의 신생혈관 생성에 관여하는 주요한 인자로 알려져 있다. 따라서 본 연구에서는 당뇨병성 망막증의 발생 기전 중 하나로 최근 연구가 진행되고 있는 VEGF의 발현과 안지오텐신 전환 효소 억제제를 이용한 VEGF 발현 억제효과의 규명을 통해 당뇨병성 망막증의 예방에 ACE 억제제가 효과가 있는지 ACE 억제제인 captopril을 이용하여 알아보고자 하였다. 본 연구에서는 streptozotocin 처리시 혈청내 VEGF 농도는 증가하였으나 captopril (65 mg/kg) 치료에 의해 감소하지 않았다. 망막에서 관찰한 결과 당뇨군에서 VEGF mRNA 및 단백질 발현이 증가하였으며, 안지오텐신 전환 효소인 capto-pril에 의해서 차단되는 것으로 나타났다. 결론적으로 captopril은 1형 당뇨에 있어서 망막의 VEGF 발현 억제를 통해 망막 보호효과를 나타내고 있음을 알 수 있었다.

• 대한임상검사과학회지
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• 제49권4호
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• pp.323-328
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• 2017

신생혈관생성은 여러 신생혈관 생성 인자들이 포함되는 중요한 과정이며, 특히 이 과정에서는 섬유아세포증식인자(FGF-2)는 세포의 증식률과 미세관 형성을 촉진하기 때문에 중요한 신생혈관 생성인자로 여겨진다. 최근 연구에 따르면 해조류에서 추출되는 후코이단 다당류 물질이 섬유아세포 증식인자2에 의한 혈관내피세포의 미세관형성을 더욱 촉진한다고 보고하였다. 그러나 섬유아세포 증식인자와 후코이단 복합처리에 따른 신생혈관생성 활성에 대한 분자적 메카니즘은 아직 연구가 부족하다. 따라서 본 연구에서는 신생혈관생성 활성을 알아보기 위하여 섬유아세포 증식인자와 후코이단 물질의 복합처리에 따른 세포의 증식과 미세관형성률 그리고 세포의 이동율을 측정하였다. 또한 이들의 신생혈관 생성 활성에 관련된 인자를 탐색하기 위하여 VEGF-A, ICAM-1, MMP9, 그리고 ICAM-1 유전자를 연전사 중합연쇄반응으로 평가하였다. 본 연구의 결과에서는 후코이단과 섬유아세포 증식인자 복합처리는 혈관내피세포의 성장률, 미세관 형성률 그리고 세포의 이동률을 촉진하고, 이 과정에서 신생혈관생성 기능과 관련된 STAT3, VEGF-A, MMP9 그리고 ICAM-1의 유전자 발현을 촉진함으로 신생혈관 생성활성이 나타나는 것으로 보여진다. 그러나 이러한 유전자 발현이 fucoidan/FGF2에 의한 angiogenic 활성 촉진에 직접적인 영향을 미치는 지에 대한 추가적인 연구가 이루어져야 할 것으로 생각된다.

• 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.

• 대한화장품학회지
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• 제49권1호
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• pp.75-85
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• 2023

본 연구에서는 7 개의 아미노산으로 이루어진 헵타펩타이드의 Lgr5 binding에 따른 인체 모낭 구성 세포의 활성에 대한 영향을 확인하였다. 표면 플라즈몬 공명(surface plasmon resonance, SPR) 시스템을 이용하여 헵타펩타이드가 Lgr5에 결합하는 것을 확인하였다. 인체 모유두세포(human hair follicle dermal papilla cell, HHFDPC)에 헵타펩타이드를 처리한 결과, 농도 의존적인 세포 증식이 나타났으며 β-catenin의 세포 내핵 이동 및 하위 유전자인 LEF1, Cyclin-D1, c-Myc의 발현 증가가 관찰되었다. 그리고 세포 증식 기전 관련 인자인 Akt와 ERK의 인산화 수준이 증가되었으며, 성장인자인 hepatocyte growth factor (HGF), keratinocyte growth factor (KGF), vascular endothelial growth factor (VEGF) 발현이 유도되었다. 또한 인체 모모세포(human hair germinal matrix cell, HHGMC)의 분화 관련 전사 인자와 인체 외모근초세포(human hair outer root sheath cell, HHORSC)의 분화 표지 인자들도 헵타펩타이드 처리 시 높은 발현율을 보였다. 추가적으로 우리는 헵타펩타이드의 인체 모낭줄기세포(human hair follicle stem cell, HHFSC) 분화에 대한 영향을 조사하였다. 그 결과, HHFSC 표지인자들의 mRNA와 단백질 수준이 감소하였고 반면에 분화 표지인자들은 증가하였다. 상기의 결과들은 헵타펩타이드가 인체 모낭 구성 세포에서 Wnt/β-catenin 경로를 촉진시켜 증식 또는 분화를 유도할 수 있음을 보여준다. 이를 토대로 종합해 볼 때, 본 연구의 헵타펩타이드는 모발 성장을 유도하고 탈모 개선에 도움을 줄 수 있는 기능성 원료로 사용될 수 있을 것으로 보인다.

• 동의생리병리학회지
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• 제24권4호
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• pp.586-591
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• 2010

Chemokine and Growth Factor are major mediumtors of immuno-inflammatory pathway. The purpose of this study is to investigate whether productions of Chemokine and Growth Factor in lipopolysaccharide (LPS)-induced mouse macrophage RAW 264.7 cells are modulated by Gallic acid (GA), which is easily founded in tannin-containing natural materials such as red wine, green tea, grape juice, and Corni Fructus. Productions of Chemokine and Growth Factor were analyzed by High-throughput Multiplex Bead based Assay with Bio-plex Suspension Array System based on $xMAP^{(R)}$ (multi-analyte profiling beads) technology. At first, cell culture supernatant was obtained after treatment with LPS and GA for 24 hour. Then, the antibody-conjugated beads were added and incubated for 30 minutes. After incubation, detection antibody was added and incubated for 30 minutes. And Strepavidin-conjugated Phycoerythrin (SAPE) was added. After incubation for 30 minutes, the level of SAPE fluorescence was analyzed on Bio-plex Suspension Array System. Based on fluorescence intensity, concentrations of Chemokine and Growth Factor were determined. The results of the experiment are as follows. GA significantly inhibited the production of interferon-inducible protein (IP)-10, keratinocyte-derived chemokine(KC), and vascular endothelial growth factor (VEGF) in LPS-induced RAW 264.7 cells at the concentration of 25, 50, 100, 200 uM (p<0.05). GA significantly inhibited the production of monocyte chemoattractant protein-1(MCP-1) and macrophage-colony stimulating factor(M-CSF) in LPS-induced RAW 264.7 cells at the concentration of 50, 100, 200 uM (p<0.05). GA diminished the production of granulocyte macrophage-colony stimulating factor (GM-CSF) in LPS-induced RAW 264.7 cells. But GA did not show the inhibitory effect on the production of leukemia inhibitory factor (LIP) and macrophage inflammatory protein (MIP)-2 in LPS-induced RAW 264.7 cells. These results suggest that GA has the immuno-modulating activity related with its inhibitory effects on the production of IP-10, KC, MCP-1, VEGF, and M-CSF in LPS-induced macrophages.

• Asian Pacific Journal of Cancer Prevention
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• 제16권6호
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• pp.2277-2281
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• 2015

Objectives: To explore the expression of astrocyte elevated gene-1 (AEG-1) in cervical cancer and analyze its correlation with microvascular density (MVD), nuclear factor kappaB (NF-kB p65) and vascular endothelial growth factor (VEGF). Materials and Methods: Immunohistochemical MaxVision method was adopted to detect the expression level of AEG-1, NF-kB p65 and VEGF in 45 samples of invading cervical cancer and 12 samples of cervicitis from The First Affiliated Hospital of Wenzhou Medical University. Tumor microvascular endothelial marker CD34 combined with Weidner was used to determine the MVD in cervical cancer tissue. The positive expression and staining conditions of AEG-1, NF-kB p65 and VEGF in cervical cancer tissues were observed under a light microscope. Correlations between expression of AEG-1 protein and those of NF-Kb p65 and VEGF, as well as MVD, were analyzed using Pearson correlation. Results: The expression levels of AEG-1 were $0.186{\pm}0.043$ in cervical cancer and $0.051{\pm}0.002$ in chronic cervicitis (p<0.01). Moreover, expression of AEG-1 was related to vascular invasion and lymphatic metastasis of cervical cancer (p<0.01), but not with age of the patients, differentiation degree, tumour size, pathological type and parametrial infiltration (p>0.05). Pearson correlation analysis showed that the expression of AEG-1 was linked with NF-kB p65 (r=0.501, p=0.000), VEGF (r=0.718, p=0.000) as well as MVD in cervical cancer tissue (r=0.815, p=0.000). Conclusions: AEG-1 is highly expressed in cervical cancer and promotes angiogenesis, which might be related to the fact that AEG-1 activating the signal pathway of NF-kB could up-regulate the level of VEGF expression.

• Tuberculosis and Respiratory Diseases
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• 제68권1호
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• pp.22-28
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• 2010

Background: Vascular endothelial growth factor (VEGF) is a potent mediator of angiogenesis. VEGF production is regulated by HIF-$1{\alpha}$ and EGFR. This study examined the relationship between the clinicopathological factors and VEGF, HIF-$1{\alpha}$ and EGFR protein overexpression, and evaluated their prognostic value in patients with a surgically resected non-small cell lung cancer (NSCLC). Methods: Patients who underwent a surgical resection at Kangnam St. Mary's hospital were reviewed retrospectively. The core biopsy samples from 54 patients with NSCLC were assembled on a tissue microarray (TMA), and immunohistochemical staining for the VEGF, HIF-$1{\alpha}$ and EGFR proteins was performed. The overexpression of these proteins was evaluated in relation to age, gender, histology and staging by univariate analysis. The clinicopathological prognostic factors were analyzed. Results: Multivariate analysis performed by Cox regression (odds ratio 2.8, 95% CI 1.0~8.2, p=0.046) revealed HIF-$1{\alpha}$ overexpression to be an unfavorable factor. There was no correlation between the overexpression of these proteins and the clinicopathological factors. VEGF showed a positive relationship with EGFR, but there was no statistical significance [$p(x^2)=0.06$]. Conclusion: HIF-$1{\alpha}$ overexpression predicts shorter survival in patients with a surgically resected NSCLC. Therefore, HIF-$1{\alpha}$ may be a poor prognostic factor in NSCLC.

• Asian Pacific Journal of Cancer Prevention
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• 제14권6호
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• pp.3419-3423
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• 2013

Of all gynecologic cancers, endometrial cancer is the most common cancer in the US and Europe. In addition, it is presently the second most common gynecologic cancer in the world. As a result of increasing menopausal, obese and tamoxifen use women, the incidence of the cancer seems to be on the increase. Surgery is the major treatment, whereas postoperative radiation therapy in high-intermediate risk patients many prevent locoregional recurrence. Adjuvant chemotherapy can improve progression free survival in advanced or recurrent cancers. Molecular targeted therapies are now a focus of attention including anti-vascular endothelial growth factor (VEGF), mammalian target of rapamycin (mTOR) inhibitor and tyrosine kinase inhibitor (TKI). They may provide useful future strategies for control of endometrial malignancies in developing countries and across the world.

• 대한두경부종양학회:학술대회논문집
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• 대한두경부종양학회 2007년도 춘계학술대회 논문집
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• pp.74-74
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• 2007