• 대한한방소아과학회지
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• 제20권1호
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• pp.181-194
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• 2006

Objective : Author evaluate the effects of Citri Reticulatae Viride Pericarpium for the bronchial asthma using assesment of the vascular endothelial growth factor after Citri Reticulatae Viride Peicarpium was intravenously administered Ovalbumine(OVA)-sensitized and -challenged mice. Material and Methods : Twenty-four female mice, 8-10 weeks old and free of murine specific pathogens, were sensitized by intraperitoneal injection of OVA. Of the sensitized mice, ten mice didn't administrate Citri Reticulatae Viride Pericarpium and the other ten mice administrated Citri Reticulatae Viride Pericarpium. Mice were sensitized on the first and fourteen days introspectional injection of 20 ${\mu}g$ OVA. After$21^{st}\;22^{th}\;and\;23^{rd}$, the initial sensitization, the mice were challenged for 30 minutes with an aerosol of 1% OVA in saline. Citri Reticulatae Viride Pericarpium administered 200mg/kg in the tail of the mouse, one a day, for 7 days and beginning 14 days after first sensitization. Bronchoalveolar lavage was performed 72 hours after the last challenge, and total cell numbers in the BAL fluid were count. Also, lever of VEGF in the BAL fluid was measured by Enzyme immunoassays and Western blot analysis. Results: Total cell numbers in BAL fluid were significantly greater than from 72 hrs after OVA inhalation compared with cell numbers in the control group. However, there was no difference of the total cell numbers between OVA-challenge groups without Citri Reticulatae Viride Pericarpium, and OVA-challenge with Citri Reticulatae Viride Pericarpium. Enzyme immunoassay revealed that VEGF levels in the BAL fluids were significantly increased 72 hrs after OVA inhalation compared with levels in the control group. After administration of the Citri Reticulatae Viride Pericarpiu, the levels of the VEGF in BAL fluids 72 hrs after OVA inhalation reduced dramatically. Western blot analysis revealed that VEGF protein levels were increased in the all mice which were challenge with OVA, without administered Citri Reticulatae Viride Pericarpium, compared the normal mouse. However, in the groups of the administered Citri Reticulatae Viride Pericarpium, the VEGF protein level markedly decreased. Conclusion: Citri Reticulatae Viride Pericarpium might affect the treatment of the bronchial ashma as a inhibition of the VEGF.

• Asian Pacific Journal of Cancer Prevention
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• 제13권6호
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• pp.2823-2828
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• 2012

Objective: To explore a new model of in-situ xenograft lymphangiogenesis of human colonic adenocarcinomas in nude mice. Method: On the basis of establishing subcutaneous xenograft lymphangiogenesis model of human colonic adenocarcinoms, in-situ xenografts were established through the in situ growth of the HT-29 human colonic adenocarcinoma cell line in nude mice. The numbers of lymphangiogenic microvessels, the expression of lymphatic endothelial cell markers lymphatic vessel endothelial hyaloronic acid receptor-1 (LYVE-1), D2-40 and the lymphatic endothelial growth factors vascular endothelial growth factor-C (VEGF-C), -D (VEGF-D) and receptor-3 (VEGFR-3) were compared by immunohistochemical staining, Western bolt and quantitative RT-PCR in xenograft in-situ models. Results: Some microlymphatics with thin walls, large and irregular or collapsed cavities and increased LMVD, with strong positive of LYVE-1, D2-40 in immunohistochemistry, were observed, identical with the morphological characteristics of lymphatic vessels and capillaries. Expression of LYVE-1 and D2-40 proteins and mRNAs were significantly higher in xenograpfts in-situ than in the negative control group(both P<0.01). Moreover, the expression of VEGF-C, VEGF-D and VEGFR-3 proteins and mRNAs were significantly higher in xenografts in-situ (both P<0.01), in conformity with the signal regulation of the VEGF-C,-D/VEGFR-3 axis of tumor lymphangiogenesis. Conclusions: In-situ xenografts of a human colonic adenocarcinoma cell line demonstrate tumor lymphangiogenesis. This novel in-situ animal model should be useful for further studying mechanisms of lymph node metastasis, drug intervention and anti-metastasis therapy in colorectal cancer.

• 대한예방한의학회지
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• 제10권2호
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• pp.51-62
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• 2006

Psoriasis is a chronic skin disease characterized by angiogenesis. It has been reported that growth factor as vascular endothelial growth factor(VEGF) and insulin like growth factor(IGF) II are overexpressed in psoriatic epidermis. To investigate the inhibitory effects of IGF-II induced VEGF and HIF-1${\alpha}$ expression by RR extracts, we performed MTS assay, western blots using HaCaT cells. RR extracts significantly reduced IGF-II induced HIF 1${\alpha}$ protein level via MAPK pathway in HaCaT cells. Also, RR extracts inhibited IGF-II induced VEGF mRNA and protein expression levels in the HaCaT keratinocytes. These results suggest that inhibition of HIF-1${\alpha}$ and VEGF expressions by RR extracts contributes to the anti angiogenic effects.

• Animal cells and systems
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• 제2권1호
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• pp.1-8
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• 1998

Hepatocyte growth factor (HGF), originally discovered and cloned as a powerful mitogen for hepatocytes, is a four kringle-containing growth factor which specifically binds to membrane-spanning tyrosine kinase, c-Met/HGF receptor. HGF has mitogenic, motogenic (enhancement of cell movement), morphogenic (e.g., induction of branching tubulogenesis), and anti-apoptotic activities for a wide variety of cells. During embryogenesis, HGF supports organogenesis and morphogenesis of various tissues, including liver, kidney, lung, gut, mammary gland, and tooth. In adult tissues HGF elicits an organotrophic function which supports regeneration of organs such as liver, kidney, lung, and vascular tissues. HGF is also a novel member of neurotrophic factor in nervous systems. Together with the preferential expression of HGF in mesenchymal or stromal cells, and c-Met/HGF receptor In epithelial or endothelial cells, the HGF-Met coupling seems to orchestrate dynamic morphogenic processes through epithelial-mesenchymal (or-stromal) interactions for organogenesis and organ regeneration. HGF or HGF gene may well become unique therapeutic tools for treatment of patients with various organ failure, through its actions to reconstruct organized tissue architectures. This review focuses on recently characterized biological and physiological functions integrated by HGF-Met coupling during organogenesis and organ regeneration.

• Asian Pacific Journal of Cancer Prevention
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• 제15권20호
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• pp.8793-8796
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• 2014

Objective: To explore the influence of serum vascular endothelial growth factor (VEGF) level on therapeutic outcome and diagnosis/prognostic value in patients with cervical cancer. Materials and Methods: A total of 37 patients diagnosed with cervical cancer by biopsy were selected and treated with concurrent chemoradiotherapy. Double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) was adopted before treatment to assess VEGF levels, and its relationships with clinicopathological features and short-term therapeutic effects were analyzed. Results: The median VEGF level in 37 patients before treatment was 647.15 (393.35~1125.16) pg/mL. Serum VEGF levels in patients aged <50 years, in International Federation of Gynecology and Obstetrics (FIGO) stage IIIa~IVa, with lymph node metastasis and tumor size >4 cm were significantly increased (P<0.05). The complete remission (CR) rate was 48.7% (18/37), partial remission (PR) rate was 35.1% (13/37), stable disease (SD) rate was 13.5% (5/37) and progressive disease (PD) rate was 2.70% (1/37), so the objective remission rate (ORR) after treatment was 83.8% (31/37). Logistic regression analysis showed that tumor size and serum VEGF level before treatment were independent risk factors affecting the therapeutic outcome, and the higher the level of serum VEGF, the worse the prognosis when tumor size>4 cm. Some 56.8% of patients manifested with myelosuppression, 37.8% with leucopenia, 24.3% with thrombocytopenia, 5.41% with diarrhea, 46.0% with nausea and vomiting, 21.6% with hair loss and 8.11% with hepatic and renal injury during the treatment. Conclusions: Serum VEGF level may reflect the degree of malignancy of cervical cancer and predict therapeutic effect, which is of great importance to cancer diagnosis and prognosis.

• 한국발생생물학회지:발생과생식
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• 제17권1호
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• pp.17-24
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• 2013

This study examined the expression of inhibitor of DNA-binding (Id) proteins and vascular endothelial growth factor (VEGF) in the ovary according to female age using a mice model as the first step in investigating the potential role of Ids and VEGF in ovarian aging. C57BL inbred female mice of three age groups (6-9, 14-16, and 23-26 weeks) were injected with 5 IU pregnant mare's serum gonadotropin (PMSG) in order to synchronize the estrus cycle. After 48 h, ovarian expression of Ids and VEGF was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR), western blot and immunohistochemistry. Ovarian apoptosis was examined by ovarian expression of Bcl-2 and Bcl-xL. Expression of Id-1 and VEGF was decreased with advancing female age, but not Id-2, Id-3, and Id-4. In particular, their expressions were significantly decreased in aged mice of 23-26 weeks compared with the young mice of 6-9 weeks (p < 0.05). In contrast, ovarian apoptosis was greatly increased in the aged mice compared to the young mice. This result suggests that Id-1 may have an implicated role in ovarian aging by associating with VEGF.

• 생명과학회지
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• 제16권7호
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• pp.1199-1206
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• 2006

Plasminogen kringle 5는 plasminogen kringles 1-4로 구성된 내생의 혈관 신생 억제제인 angiostatin과 같이 내피세포의 분열을 강력하게 억제한다고 알려져 있다. 본 연구에서는 plasminogen kringle 5의 재조합 단백질을 효모 발현 체계에서 생산하여 내피세포의 이동에 대한 저해 효과와 이에 대한 작용기전을 조사하였다 재조합 단백질 PK5는 plasminogen의 Thr456에서 Phe546까지 이르는 cDNA 부분을 ${\alpha}-factor$ prepro-peptide의 분비 신호 서열 뒤에 도입하여 Pichia pastoris GS115에서 발현시켰다. 메탄올 유도 후 얻은 배양액을 S-spin column을 이용하여 정제하였다. 정제된 단백질을 SDS-PACE하였을 때 약 10kDa의 단일 밴드를 나타냄을 확인할 수 있었다. 정제된 PK5는 bFGF나 VEGF에 의해 유도된 인간의 제대 유래 내피 세포의 이동을 약 500nM의 $IC_{50}$ 값으로 농도 의존적으로 감소시켰다. 내피 세포에 PK5 500M을 처리한 결과 bFGF에 의해 유도된 ERK1/2의 인산화를 감소시켰다 또한, PK5는 bFGF에 의해 유도된 내피세포의 골격 재형성을 강력하게 억제하는 것으로 관찰되었다. 따라서, 이러한 결과들은 효모 생산 PK5가 내피세포의 이동을 효과적으로 억제하며, 이는 ERK1/2의 활성과 세포골격의 재배열을 억제함으로써 나타나는 것으로 부분적으로 설명될 수 있다.

• 한국응용과학기술학회지
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• 제37권2호
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• pp.354-361
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• 2020

본 연구는 규칙적인 태권도 트레이닝이 비만 중년 여성의 뇌신경성장인자 및 인지기능에 미치는 영향을 알아보는데 목적이 있었다. 본 연구를 위하여 중년 비만 여성 33명이 연구대상자로 선정되었으며, 연구대상자들은 태권도 그룹(TG, n=15)과 대조그룹(CG, n=18)에 무선 배정되었다. 태권도 그룹은 16주간 일주일에 5번 태권도 트레이닝을 실시하였으며, 두 그룹 모두 트레이닝 전과 후 각각 brain-derived neurotrophic factor(BDNF), vascular endothelial growth factor(VEGF), insulin-like growth factor-1(IGF-1) 농도 검사와 Stroop Color and Word test를 실시하였다. 연구 결과 태권도 그룹의 BDNF와 IGF-1이 트레이닝 후 유의하게 증가한(p<.05) 반면 VEGF와 Stroop Color and Word Test 결과는 유의한 차이가 나타나지 않아 규칙적인 태권도 트레이닝이 비만 중년 여성의 뇌신경영양인자에는 긍정적이지만 뇌 인지기능에는 영향이 없는 것으로 나타났다.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제32권1호
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• pp.8-18
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• 2006

Purpose: The purpose of this study was to verify that the expressions of angiogenin, transforming growth factor-beta(TGF-${\beta}$), vascular endothelial growth factor(VEGF), human apurinic/apyrimidinic endonuclease(APEX) and tumor necrosis factor-alpha(TNF-${\alpha}$) were associated with the tumorigenesis of the oral squamous cell carcinoma(OSCC). Materials and Methods: Fifty-one samples of OSCC and fifteen normal oral mucosae were obtained to analyze the expression levels of above five factors. mRNA expressions were quantified by the quantitative competitive PCR(QC-PCR) method. After 2% agarose gel electrophoresis stained with ethidium bromide, the concentration of mRNA was calculated by a digital image analysis system. The expression levels of angiogenin, TGF-${\beta}$, VEGF, APEX and TNF-${\alpha}$ were compared by unpaired Student's t-tests between cancer and normal tissues. We analyzed statistically to find the cut-off values that would be useful as diagnostic markers, and the linear regression analysis between every two factors of these five factors by SAS system. Results: All of these five factors (angiogenin: P<0.0037, TGF-${\beta}$: P<0.0001, VEGF: P<0.0102, APEX: P<0.0023, TNF-${\alpha}$: P<0.0074) were significantly correlated with OSCC. In the analysis to find the cut-off values for the diagnosis, we could not find any value that had a reasonable sensitivity and specificity. In the linear regression analysis, there were correlations between angiogenin and TNF-${\alpha}$, TGF-${\beta}$ and VEGF, TGF-${\beta}$ and APEX, TGF-${\beta}$ and TNF-${\alpha}$, VEGF and APEX, VEGF and TNF-${\alpha}$, APEX and TNF-${\alpha}$. Conclusion: Our results suggest that not only angiogenin, TGF-${\beta}$, VEGF, APEX and TNF-${\alpha}$ are significantly associated with the tumorigenesis, but also the close relationship between these factors might enhance the tumorigenesis of OSCC. We can not find clinical availability for diagnosis.

• Asian Pacific Journal of Cancer Prevention
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• 제15권6호
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• pp.2491-2494
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• 2014

Objective: To explore the mechanism and significance of tumor angiogenesis by observing changes of microvessel density (MVD) and expression of vascular endothelial growth factor (VEGF) in residual tumor tissues after cryoablation. Materials and Methods: A total of 18 nude mice xenograft models with transplanted lung adenocarcinoma cell line A549 were established and randomly divided into 3 groups when the maximum diameter of tumor reached 1 cm: control, cisplatin (DDP) and cryoablation. The nude mice were sacrificed after 21-d cryoablation to obtain the tumor tissues. Then immunohistochemistry was applied to determine MVD and the expression of VEGF in tumor tissues. Results: The tumor volumes of control group, DDP group and cryoablation group were $1.48{\pm}0.14cm^3$, $1.03{\pm}0.12cm^3$ and $0.99{\pm}0.06cm^3$ respectively and the differences were significant (P<0.01), whereas MVD values were $21.1{\pm}0.86$, $24.7{\pm}0.72$ and $29.2{\pm}0.96$ (P<0.01) and the positive expression rates of VEGF were $36.2{\pm}1.72%$, $39.0{\pm}1.79%$ and $50.8{\pm}2.14%$ (P<0.01), respectively, showing that MVD was proportional to the positive expression of VEGF (r=0.928, P<0.01). Conclusions: Cryoablation can effectively inhibit tumor growth, but tumor angiogenesis significantly increases in residual tumors, with high expression of VEGF playing an important role in the residual tumor angiogenesis.