• Proceedings of the Korean Society of Applied Pharmacology
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• 1993.04a
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• pp.146-146
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• 1993

신장에서 브라디키닌(Bradikinin, BK)의 생리적 역할을 규명하기 위한 첫 단계로 토끼신장 근위세뇨관의 일차배양세포를 이용, BK 수용체를 ($^3$H) BK를 이용하여 수용체결합실험을 함과 아울러 세포배양과정에서 여러 성장인자들의 BK 수용체발현에 미치는 영향을 관찰하였다. 첫째, 토끼 신장의 피질, 수질 및 근 위세뇨관 둥 각 부위에 대한 BK 수용체결합 실험결과 신수질 부분에 가장 많은 BK 수용체가 발견되었으며 이때 해리항수는 0.52 nM, 그리고 최대결합부위는 mg 단배질당 112.5 fmol이었다. 둘째, serum free 배지에서 insulin, transferrin 그리고 hydrocortisone이 성장인자로 사용될 때 BK 수용체발현이 가장 높았으며 이 중 인슐린에 가장 큰 영향을 받았다. 한편 인슐린의 최적농도를 결정하는 실험의 결과 5 $\mu\textrm{g}$/ml매서 가장 높은 수용체발현을 나타내었으며 그 이상에서는 별다른 차이를 보이지 못했다. 세째, 위의 세 성장인자에 prostaglandin E$_1$이나 triiodothyronine을 첨가시 BK 수용체발현은 오히려 저하되었다. 네째, fetal bovine serum (FBS)과 위의 세 성장인자간의 수용체발현능을 비교한 실험에서 세포배양 후 첫 일주일에는 FBS가 세 성장인자보다 약간 나은 수용체발현능을 나타내었으나 그후 이주째에는 세 성장인자가 BK 수용체발현에 더 적절한 요소임을 보여주었다. 이상의 결과로 보아 토끼 근위세뇨관 상피세포에서의 BK 수용체발현은 세포성장인자로 insulin, transferrin, hydrocortisone 중 insulin에 가장 큰 영향을 받는것으로 보이며, 이들 세가지 성장인자는 serum free 배지에서 세포성장 및 기능에 많은 영향을 주는 것으로 생각된다.prolidine이 $K_{M}$ /K$_{H}$ 비가 가장 높았고 diphenidol이 가장 낮았다. 이상의 결과로 보아 항 histamine제의 muscarinic receptor 차단작용은 이들 약물의 항 alleragy 효과에 필요한 작용이 아니며 본 실험에서 추정된 항 histamine제의 H$_1$-receptor와 muscarinic receptor에 대한 상대적 역가는 이들 약물의 선택과 평가에 중요한 지표가 될수 있을 것으로 생각된다.ing ischemic insults. The nature of the receptor is being explored by molecular genetic techniques, and we have recently cloned two of the major subunits; some of the data will be presented.LIFO, 우선 순위 방식등을 선택할 수 있도록 확장하였다. SIMPLE는 자료구조 및 프로그램이 공개되어 있으므로 프로그래머가 원하는 기능을 쉽게 추가할 수 있는 장점도 있다. 아울러 SMPLE에서 새로이 추가된 자료구조와 함수 및 설비제어 방식등을 활용하여 실제 중형급 시스템에 대한 시뮬레이션 구현과 시스템 분석의 예를 보인다._3$", chain segment, with the activation energy of carriers from the shallow trap with 0.4[eV], in he amorphous regions.의 증발산율은 우기의 기상자료를 이용하여 구한 결과 0.05 - 0.10 mm/hr 의 범위로서 이로 인한 강우손실량은 큰 의미가 없음을 알았다.재발이 나타난 3례의 환자를 제외한 9례 (75%)에서는 현재까지 재발소견을 보이지 않고 있다. 이러한 결과는 다른 보고자들과 유사한 결과를

• The korean journal of orthodontics
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• v.27 no.2
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• pp.349-357
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• 1997

Epidermal growth factor(EGF), a single chain polypeptide of 53 amino acids with a molecular weight of 6,045 Da, was first isolated from the male mouse submandibular glands. EGF stimulates cellular proliferation and differentiation in several tissues and accelerates the rate of wound healing. EGF is bound to the specific receptor(EGFR) on the cell membrane of its target cell. EGFR is a transmembrane glycoprotein with a molecular weight of 170,000 Da and is detectable on a large variety of cell types and tissues. The authors investigated the expression of EGFR in the normal and inflamed human gingival epithelium to study the role of EGFR in the inflammation of the gingival epithelium, and the expression of EGFR in the dental follicle by using in situ mRNA hybridization and immunohistochenistry. The results weree as follows : 1. The expression of EGFR mRNA in the normal gingival epithelium on in situ mRNA hybridization was mainly localized on the basal cell layer, and the spinous layer was weakly positive The granular and cornified layers were negative 2. The expression of EGFR protein in the normal gingival epithelium on inmunohistochemistry was localized on the cornified and granular layers, and the spinous layer was weakly positive. The basal cell layer was completely negative 3. The expression of EGFR mRNA in the inflamed gingival epithelium on in situ mRNA hybridization was evenly and homogeneously distributed in the whole layers of the gingival epithelium except the cornified layer. The staining intensity appeared to increase progressively from the basal cell layer to the cornified layer. 4. The expression of EGFR protein in the inflamed gingival epithelium on immunohistochemistry was evenly and homogeneously distributed in the whole layers of the gingival epithelium. The staining intensity appeared to increase progressively from the cornified layer to the basal cell layer. 5. Strong positive reaction was seen in the epithelial cell rests of Malassez, whereas only background staining was seen in other cells of the dental follicle. In conclusion, the up-regulation of EGFR in the inflamed gingival epithelium and the high amounts of EGFR in the epthelial cell rests of Malassez in the dental follicle can be regarded as responses to the possible damages to the oral environment to maintain the homeostatic conditions.

• 대한두경부종양학회:학술대회논문집
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• 1992.11a
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• pp.131.1-131.1
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• 1992

• The korean journal of orthodontics
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• v.28 no.5 s.70
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• pp.775-782
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• 1998

The purpose of this study is to investigate the change of the EGFR mRNA expression in the rat gingival epithelium by the experimental tooth movement. We applied reciprocal force between the upper anterior teeth using NiTi open coil spring and stainless steel wire for 1, 2 3, 7 days. For the detection of EGFR mRNA, in situ hybridization was done in the tissue samples which were taken from the pressure and tension sides of teeth. The results were as follows ; 1. The expression of EGFR mRNA was increased application-time dependently. a. Day 1 mild expression on the basal and spinous cell layers b. Day 2 . moderate expression on the whole layers c. Day 3 : severe expression on the basal and spinous cell layers 4. Day 7 severe expression on the whole layers 2. The expression level of EGFR mRNA in the pressure and tension sides were similar during the whole Period of experiment except seven day application at which the cornified layer of the tension side showed moderate expression. 3. Removal of the appliance after 7-day force application lowered the level of EGRF mRNA expression. It was returned to the mild and control (rare) level at three and seven days after the removal, respectively. In conclusion, EFGR mRNA was increased by the experimental tooth movement on the rat ginigval epithelium. Up-regulation of EGFR mRNA in the gingival epithelium can be regarded as responses to the possible changes caused by the physical stersses to the oral environment to maintain the homeostatic conditions of the periodontium.

• Journal of Dairy Science and Biotechnology
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• v.34 no.1
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• pp.1-7
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• 2016

Colostrum, a nutrient-rich fluid produced by female mammals after giving birth, is the specific initial diet of mammalian neonates. Colostrum is important for the nutrition, growth, and development of newborn infants and contributes to the immunologic defense of neonates. It contains immunoglobulins, antimicrobial peptides, such as lactoferrin and lactoperoxidase, and other bioactive molecules, including growth factors, such as IGF (insulin-like growth factor), EGF (epithermal growth factor), $TGF-{\beta}$ (transforming growth factor), and FGF (fibroblast growth factor). Bovine colostrum is a rich source of growth factors, which play a central role in wound healing. The biological activities of colostrum emphasize the relevance of the synergistic activity of growth factors to stimulate keratinocyte proliferation and migration, which are essential for tissue repair. Colostrum increases the expression of early differentiation markers, such as keratin 1 and 10 and involucrin, and late differentiation markers, including loricrin and filaggrin. Additionally, colostrum increases granulation tissue volume in the dermis, suggesting that it has a beneficial effect on wound healing. The therapeutic use of colostrum or individual peptides present in colostrum has a positive and curative influence on various gastrointestinal diseases.

• Proceedings of the Korean Society of Developmental Biology Conference
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• 2003.10a
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• pp.66-66
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• 2003

Protein tyrosine kinases는 표적단백질의 tyrosine 잔기를 인산화하는 효소로서 다양한 종류의 성장인자, peptide 호르몬, cytokine 수용체 하위의 세포 내 신호전달에 관여한다. Non-receptor tyrosine kinase의 일종인 c-Src는 세포막에서 발생한 ligand-receptor 상호작용 하위의 신호전달에서 중요한 역할을 하며 C-terminal Src kinase (Csk)는 Src kinase의 C-terminal tyrosine 잔기를 인산화시켜 Src kinase의 활성을 저해한다. 이러한 Src-Csk loop를 통한 세포 내 신호전달과정은 세포의 증식과 분화, 사멸 조절에 중요한 기능을 갖지만 정소의 발생과 분화 과정에서 Src-Csk loop의 발현 및 정자형성 과정에서의 기능은 밝혀지지 않았다. 본 연구에서는 생쥐 정소에서 출생 후 성적 성숙과정에서 Csk의 발현과 Src kinase 활성의 변동을 조사하였다. Csk mRNA 발현은 생 후 2주령 이하의 미성숙 정소에서 다량으로 발현되었고 사춘기 정소 이후에는 오히려 감소하였다. Csk 단백질의 발현 양상은 mRNA 발현양상과 일치하였다. c-Src kinase 활성은 생 후 2주에 급격히 증가하고 이 후 4주령에서 감소하다가 성체 (8주령)에서 다시 증가하여 가장 높았다. 성체 조직의 Csk 단백질 현존량이 미성숙 개체보다 적은 반면 Src kinase 활성은 가장 높아 Csk 발현의 감소는 Src kinase 활성을 증가하는 것으로 사료된다. 면역조직화학방법으로 정소 조직 내 Csk의 발현양상을 조사한 결과 Leydig cell, Sertoli cell, germ cell 등 도처에서 발현되었으며 Sertoli cell 에서의 발현은 세정관 상피의 구성에 따른 차이가 확인되었다. 성체의 세정관 내에서는 감수분열 이후의 정세포(spermatid)를 감싸고 있는 Sertoli cell의 강소측에서 강한 Csk 활성이 검출되어 생식세포의 분화과정 동안 세정관 상피의 조직재구성에 관여하는 것으로 사료된다. Leydig cell에서의 발현은 생후 1주령까지는 미미하였으나 이후 2주령 이후에는 다량으로 발현함이 확인되어 adult type Leydig cell에서 진행되는 steroidogenesis와의 관련성을 추측할 수 있다. 미성숙 정소로부터 분리한 Sertoli cell-enriched culture에 200 nM testosterone을 처리하였을 때 Csk mRNA의 발현의 증가를 확인할 수 있었으므로 androgen에 의한 Sertoli cell의 분화과정에 Csk가 관여하고 있음을 알 수 있다. 결론적으로 성적 성숙에 따른 생쥐 정소 내 Src-Csk loop의 발현과 Src kinase 활성의 변동은 정소 내 간충조직, 세정관 상피의 증식 및 기능적 분화 과정을 매개하는 생리적 활성분자 수용체 하위의 신호전달 과정에 Src-Csk loop에 의한 조절가능성을 확인할 수 있었다.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.28 no.3
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• pp.193-201
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• 2006

Squamous cell carcinoma(SCC) of head and neck(SCCHN) is the sixth most common human malignant tumor. However, despite advances in prevention and treatment of SCC, the five-year survival rates for patients remain still low. To improve the outcome for patients with SCCHN, novel treatment strategies are needed. Overexpression of the epidermal growth factor(EGF) and activation of its receptor(EGFR) are associated with progressive growth of SCCHN. Vascular endothelial growth factor(VEGF) signaling molecules are related with neoangiogenesis and vascular metastasis of SCC. In this study, we determined the therapeutic effect of AEE788(Novartis Pharma AG, Basel, Switzerland), which is a dual inhibitor of EGFR/ErbB2 and VEGFR tyrosine kinases, on human oral SCC. At first, we screened the expression of EGFR, c-ErbB2(HER-2) and VEGFR-2 in a series of human oral SCC cell lines. And then we evaluated the effects of AEE788 on the phosphorylation of EGFR and VEGFR-2 in a oral SCC cell line expressing EGFR/HER-2 and VEGFR-2. We also evaluated the effects of AEE788 alone, or with paclitaxel(Taxol) on the oral SCC cell growth and apoptosis. As a result, all oral SCC cells expressed EGFR and VEGFR-2. Treatment of oral SCC cells with AEE788 led to dose-dependent inhibition of EGFR and VEGFR-2 phosphorylation, growth inhibition, and induction of apoptosis. Moreover, AEE788 sensitizes the cells to paclitaxel-mediated toxicity and apoptosis. These data mean EGFR and VEGFR-2 can be reliable targets for molecular therapy of oral SCC, and therefore warrant clinical use of EGFR/VEGFR inhibition in the treatment of patients with recurrent or metastatic oral SCC.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.31 no.1
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• pp.8-17
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• 2009

Purpose: We determined the therapeutic effect of an epidermal growth factor receptor (EGFR)-specific monoclonal antibody (mAb), cetuximab (Erbitux) on the growth of oral squamous cell carcinoma (OSCC) xenografted in athymic nude mice. Experimental Design: We induced subcutaneous tumors by inoculating human tumor cell suspension into the right flank of nude mice. Nude mice with subcutaneous tumors were randomized to receive cetuximab alone, paclitaxel alone, cetuximab plus paclitaxel, or a placebo (control). Antitumor mechanisms of cetuximab were determined by immunohistochemical and apoptosis assays. Results: Cetuximab, paclitaxel, and cetuximab/paclitaxel combined therapy resulted in 50%, 52%, 67% in vivo inhibition of tumor proliferation, respectively. Tumors of mice treated with cetuximab plus paclitaxel demonstrated decreased PCNA-positive tumor cells and increased apoptotic tumor cells, which slowed growth of the murine tumors. Conclusion: These data show that EGFR can be a molecular target for the treatment of OSCC. And combination therapy with cetuximab and paclitaxel warrants further clinical study.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.45 no.2
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• pp.175-184
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• 2019

The epidermal growth factor (EGF) has a intrinsic function of inducing growth and proliferation of cells through interacting with cell membrane receptors in human epidermis and dermis layer. These functions of EGF are used as a main ingredient for wound healing medicines and anti-aging cosmetics. As a cosmetic ingredient, the EGF has a problem in exhibiting its natural efficacy due to the lack of the ability to penetrate through the stratum corneum, which is known as the skin barrier. In this study, a recombinant human epidermal growth factor ($MTD_{151}-EGF$) fused with the macromolecule transduction domain $(MTD)_{151}$ with the skin penetration ability was developed to improve the skin penetration efficiency of the EGF. Expression of $MTD_{151}-EGF$ was performed in E. coli transformed with a vector encoding the $MTD_{151}-EGF$ gene and then purified. The purified $MTD_{151}-EGF$ was evaluated using cell proliferation assay, cytotoxicity test and skin penetration test by franz diffusion cell assay and artificial skin. Cell proliferation activity of $MTD_{151}-EGF$ purified to high purity of 99% or above was equivalent to the EGF or better, and cytotoxicity was not observed. In addition, the $MTD_{151}-EGF$ showed an excellent penetration efficiency compared to the EGF in the skin penetration test with EGF and $MTD_{151}-EGF$ labeled by FITC in an artificial skin penetration model. Based on the quantitative analysis of the penetrating substance using franz diffusion cell assay, the amount of penetration was about 16 times more than that of EGF. These results can be regarded as an effective alternative to improve the existing physical transdermal penetration method related to the use of various active ingredients for cosmetics.

• Proceedings of the KOR-BRONCHOESO Conference
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• 1993.05a
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• pp.85-85
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• 1993

The clinical staging system for laryngeal cancers is not sufficient for prognosticator due to different biologic characteristics and their microenvironment according to primary sites. For determining the prognosticators, the authors peformed immunohistochemical staining to EGFR, p53 protein, and pRB in 40 cases of surgically treated squamous cell carcinomas of larynx in our institute during the past 5 years. The results are as followings; 1. The positive expression rate of p53 protein and negative expression rate of pRB showed correlations with clinical parameters. 2. The three-year survival rate for p53 protein positive cases was worse than the p53 protein negative cases. 3. Expression rate of EGFR was not correlated with the clinical parameters. As a conclusion, expression rates of p53 protein and pRB not only reflect well the biologic behavior of laryngeal cancer, but correlate closely with the tumor factors. Therefore they may be useful as the prognosticator to predict the malignant potency of laryngeal squamous cell carcinomas.