• 한국미생물·생명공학회지
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• 제24권5호
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• pp.553-559
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• 1996

We have designed nucleotide sequences of hEGF structural gene to eliminate the N-terminal methionine residue incorporated during the translation initiation step, and constructed recombinant human epidermal growth factor (rhEGF) secretion plasmids pYHB101, and pYHB2 in which pelB signal sequence-hEGF gene was expressed under the control of the T7, and tac promoter, respectively. We also constructed pYHB1 vector which contains rhEGF gene controlled by T7 promoter. The transformant with pYHB101 showed relatively slow growth pattern compared to the transformant with pYHB1. However, we observed that the transformant with pYHB101 secreted rhEGF of 13 mg/l significantly after 5 hr induction with 1 mM IPTG and that the T7 promoter was more effective than tac promoter when connected to pelB signal sequence. The amount of rhEGF was 14 mg/l under the sub-optimized condition.

• Journal of Chest Surgery
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• 제34권2호
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• pp.138-147
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• 2001

배경: 폐암발생에 EGF의 자가 분비는 암의 성장과정에 직, 간접적인 영향을 주고 있으며, TNF-$\alpha$는 면역 반응의 급성체로서 폐암의 발생을 억제하고 이미 발생한 폐암종의 치료에도 이용되고 있는 실정이다. 폐암 조직과 혈장에서 epidermal growth factor(EGF)와 tumor necrosis factor-$\alpha$(TNF-$\alpha$)를 면역 방사선 분석법을 이용하여 정량분석 하여 발현 정도를 분석해보고자 하였다. 대상 및 방법: 폐암환자 20례와 양성종양 및 육아종 환자 4례에 대해서 AJCCS에 의한 조직학적 분류와 TNM 분류에 따라 구분하여 절제수술을 받은 환자를 대상으로 수술전 혈액을 채취하고 수술직후 적출한 표본을 암이 없는 건강하다고 판단되는 대조조직과 폐암조직에서 일정량의 조직을 절취하여 액화질소 내에 실험시까지 급속 냉동보관 하였다. 수술후 혈액을 재 채취하여 혈장을 분리하여 냉동고에 검사시까지 보관하였다. EGF의 정량은 Human Epidermal Growth Factor kit(Amersham Phamacia Biotech, England)를 사용하였으며, TNF-$\alpha$ 정량은 TNF-$\alpha$ IRMA kit(Biosouce, Belgium)을 사용하여 IRMA 방법으로 각각 정량분석하여 표현유무를 연구한 결과 다음과 같은 결론을 얻었다. 결과: 1. 대조조직, 양성종양 및 육아종과 폐암 수술전후의 조직과 혈청 모두에서 EGF와 TNF-$\alpha$가 발현되었다. 2. EGF와 TNF-$\alpha$의 농도는 대조조직과 양성종양(0.11$\pm$0.06 ng/ml, 20,3$\pm$9.08 pg/ml)에 비하여 폐암조직(0.13$\pm$0.05 ng/ml, 34.34$\pm$47.74pg/ml)에서 유의하게 높은 농도가 발현되고 있었다. 3. 폐암중 선암조직에서 특히 TNF-$\alpha$(80.92$\pm$104.08 ng/ml)의 발현이 강하게 나타났다. 4. 혈청내의 EGF와 TNF-$\alpha$의 발현되는 양이 조직내의 양보다도 높았다. EGF는 5.7배정도 TNF는 1.3배정도 강하게 표현되었다. 5. 폐암의 조직학적 종류에 따라서 EGF는 거의 차이가 없었으나 TNF-$\alpha$ 정량치에는 차이가 있었다. 6. TNM stage가 진행함에 따라 EGF는 농도가 증가하였고 TNF-$\alpha$는 오히려 감소하는 반대되는 교차현상이 있었다. 7. 수술직후 EGF는 증가하였으나 TNF-$\alpha$는 오히려 감소하였다. 결론: 결론적으로 저자는 암조직과 대조조직간에 EGF와 TNF-$\alpha$의 표현량의 차이가 있음을 관찰하였으며 또한 조직과 혈청사이에도 표현량에 차이가 있으며 조직보다도 오히려 혈청내의 농도가 높다는 사실을 관찰하였다. EFG와 TNF-$\alpha$는 정상조직이나 양성조직과 폐암조직 모두에서 분비작용되는 cytokines으로 세포기능에 따라 다양하게 표현이 되며 계속적인 연구로서 밝혀야만 할 과제라고 판단된다.

• 대한약학회:학술대회논문집
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• 대한약학회 2001년도 Proceedings of the Pharmaceutical Society of Korea
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• pp.223.1-223.1
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• 2001

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제26권2호
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• pp.154-163
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• 2000

Growth factors and the receptors play an important role in the regulation of the growth and development of mammalian cells. In particular, epidermal growth factor is a polypeptide with potent mitogenic activity that stimulates proliferation of various normal and neoplastic cells through the interaction with its specific receptor(EGFR). EGFR has been described as a parameter of poor prognosis in many human neoplasms such as breast, bladder, and vulvar cancers. The objectives of this study are the evaluation of the expression of EGFR and cell cycle analysis in the head and neck squamous cell carcinomas(SCC), and the evaluation of the correlation between clinico-patholgic features and expression of EGFR and S-phase fraction. 37 head and neck squamous cell carcinoma specimens were evaluated for expression of EGFR by Western blot analysis and S-phase fraction by cell cycle analysis using the flow cytometry. The obtained results were as follows : 1. The expressions of EGFR were observed in 20 specimens(54%) among 37 head and neck SCC specimens. In case of oral SCC, 15 specimens(56%) out of 27 specimens were observed, and in case of nasopharyngeal SCC 5 specimens(50%) out of 10 specimens. 2. There was no correlation between clinical features(location, stage) of head and neck SCC and expression of EGFR (p>0.05). 3. There was a significant correlation between histo-pathological differentiation of head and neck SCC and expression of EGFR (p<0.02). 4. There was a significant correlation between expression of EGFR and S-phase fraction of cell cycle in the head and neck SCC (p<0.05). The above results suggest that expression of EGFR and S-phase fraction of cell cycle are adjunctive prognostic marker in the head and neck squamous cell carcinomas.

• 한국수정란이식학회:학술대회논문집
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• 한국수정란이식학회 2002년도 국제심포지엄
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• pp.34-36
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• 2002

Epidermal growth factor (EGF) and insulin-like growth factor-I (IGF-I) have been shown to stimulate proliferation and differentiation of various somatic cells, including placental trophoblasts and also to enhance fetal growth and development when maternally administered. Since an increase of the expression of placental EGF and IGF-I receptors in rat, mouse, and human with the gestation advanced, both EGF and IGF-I were considered to play pivotal roles on fetal growth by regulating some function of placental cells. Amino acids are crucial importance for both maternal and fetal requirements of energy source and essential constituent of fetal mass during pregnancy. Impaired fetal and placental uptake of amino acids has been observed in several models of growth retardation in the rat. Amino acid is concentrated in the fetal side through active transport by amino acid transporters and is one of the important metabolic fuels for the fatal growth. Therefore, at first plasma amino acid concentrations in mothers and fetuses were measured as an index of uphill transport across the placenta associated with EGF and IGF-1. The EGF administration at the concentration of 0, 0.1, or 0.2 $\mu\textrm{g}$/g to pregnant rats from day 18 to 21 of gestation apparently increased fetal/maternal ratio of serum proline concentration and also fatal growth in EGF dose-dependent manner. When IGF-I in doses of 0, 1, 2, and 4 $\mu\textrm{g}$/g were administrated, the ratio of leucine, isoleucine, tryptophan, phenylalanine, tyrosine and also fetal growth significantly increased with a dose-dependent manner. These results suggested that EGF and IGF-I enhanced fatal growth by, as one of its possible mechanisms, promoting placental activity to transfer some amino acid supplies from the mother to the fetus in late pregnancy.

• Biomolecules & Therapeutics
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• 제18권4호
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• pp.396-401
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• 2010

We conducted this study to investigate whether baicalin, baicalein or schizandrin significantly affect MUC5AC mucin production induced by epidermal growth factor (EGF) or phorbol ester (PMA) in human airway epithelial cells. Confluent NCI-H292 cells were pretreated with varying concentrations of baicalin, baicalein or schizandrin for 30 min and then stimulated with EGF or PMA for 24 h, respectively. MUC5AC mucin protein production was measured by ELISA. The results were as follows: (1) Baicalin was found to inhibit the production of MUC5AC mucin protein induced by both EGF and PMA. (2) Baicalein, the aglycone of baicalin, also inhibited MUC5AC mucin production. (3) Schizandrin, derived from Schizandrae Fructus, inhibited MUC5AC mucin production by the same inducers. These results suggest that baicalin, baicalein and schizandrin can regulate the production of mucin protein by directly acting on human airway epithelial cells.

• Archives of Pharmacal Research
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• 제28권8호
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• pp.988-994
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• 2005

The purpose of the present study was to prepare multivesicular liposomes with a high drug loading capacity and to investigate its potential applicability in the oral delivery of a peptide, human epidermal growth factor (rhEGF). The multivesicular liposomes containing rhEGF was prepared by a two-step water-in-oil-in-water double emulsification process. The loading efficiency was increased as rhEGF concentration increased from 1 to 5mg/mL, reaching approximately $60\%$ at 5 mg/mL. Approximately $47\%$ and $35\%$ of rhEGF was released from the multivesicular liposomes within 6 h in simulated intra-gastric fluid (pH 1.2) and intra-intestinal fluid (pH 7.4), respectively. rhEGF-loaded multivesicular liposomes markedly suppressed the enzymatic degradation of the peptide in an incubation with the Caco-2 cell homogenate. However, the transport of rhEGF from the multivesicular liposomes to the basolateral side of Caco­2 cells was two times lower than that of the rhEGF in aqueous solution. The gastric ulcer healing effect of rhEGF-loaded multivesicular liposomes was significantly enhanced compared with that of rhEGF in aqueous solution; the healing effect of the liposomes was comparable to that of the cimetidine in rats. Collectively, these results indicate that rhEGF-loaded multivesicular liposomes may be used as a new strategy for the development of an oral delivery system in the treatment of peptic ulcer diseases.

• 생명과학회지
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• 제18권2호
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• pp.279-283
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• 2008

12.6살 된 수컷 Shitzu의 항문주위에 형성된 결절 조직의 생검을 실시하였다. 육안적 소견상 결절은 갈색과 검은색을 나타냈으며 절단면은 흰색의 균질한 물질로 가득 차 있었으며 일부에서는 괴사소견을 관찰 할 수 있었다. 광학적 현미경 상에서 종양세포들은 농축된 핵을 가지고 있으며 일부에서는 원시 종양세포들이 인접 조직을 침습하고 있는 것을 관찰할 수 있었다. 또한 면역조직 화학적 염색상에서 농축된 종양세포, 주변조직에 침습한 종양세포와 기저세포는 EGFR, HER-2/neu, MMP-9, PKC ${\alpha}$ 등에 양성반응이 나타난 것을 관찰되었다. 일반적으로 개에서의 양성 항문주위선종은 다른 종양보다 4.5배 이상 발생된다는 보고(특히 수캐)가 있으나 조직병리학적 소견과 면역화학적 염색소견상 전형적인 항문주위선 샘암종은 보기 드물게 나타나므로 향후의 종양진단과 종양연구에 도움이 될 것으로 사료된다.

• Radiation Oncology Journal
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• 제24권1호
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• pp.67-76
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• 2006

목적 : 구내염은 두경부종양이 있는 암환자에게 방사선 및 항암제 치료 시술 시 매우 흔하게 발생하는 합병증이다. 본 연구는 Rat 의 방사선성 구내염 모델에서 recombinant human epidermal growth factor (rhEGF)의 효과를 평가하고자 하였다. 대상 및 방법: 25 Gy의 방사선량으로 두부에 단회 조사한 Rat를 무작위로 7마리씩 무처치군, 부형제 처치군, rhEGF 15 또는 $30{\mu}g/day$ 구강 내 처치군으로 나누었으며, 방사선을 조사하지 않은 7 마리의 Rat를 정상시험군으로 나누었다 rhEGF 시료 및 부형제는 1일 3회 Rat 의 구강점막에 매일 도포하였다. Rat의 생존율, 체중변화 및 사료섭취량을 18일 동안 관찰하였으며, 방사선 조사 후 7 일 및 18 일째에 Rat의 구강점막을 조직학적으로 평가하였다. 결과 : 실험종료 시점에서 rhEGF 15 또는 $30{\mu}g/day$ 구강 내 처치군이 모두 33%의 생존율을 보인 것에 비하여, 무처치군 및 부형제 처치군은 모두 0%의 생존율을 보였다. 체중변화에서도 rhEGF 처치군은 방사선 조사 후 2일부터 7일까지 부형제 처치군에 비하여 Rat 의 평균체중이 통계적으로 더욱 무거웠다 사료섭취율은 모든 시험군에서 방사선 조사 후 4 일까지 감소하는 양상을 보이다가, rhEGF 15 또는 $30{\mu}g/day$ 구강 내 처치군에서 14일째에 뚜렷한 사료섭취율의 증가가 관찰되었다. 방사선 조사 후 7 일째의 조직학적 분석 결과, rhEGF 15 또는 $30{\mu}g/day$ 구강 내 처치군의 Rat 에서는 점막 표피층의 각질세포의 종창 및 변성만이 관찰되었던 것에 비하여, 무처치군 및 부형제 처치군에서는 심한 위막성 또는 궤양성 구내염이 관찰되었다. 결론; rhEGF (15 또는 $30{\mu}g/day$ 구강 내 처치군) 처치에서 방사선 조사로 유발시킨 Rat의 구내염 모델에서 유의성 있는 치유 효과를 확인하였으며, 본 시험결과로 rhEGF가 방사선에 의해 유발된 구내염을 치료할 수 있는 임상 제제로써의 가능성을 볼 수 있었다.

• International Journal of Oral Biology
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• 제43권3호
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• pp.161-169
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• 2018

We previously demonstrated that epidermal growth factor (EGF) enhances cell migration and invasion of breast cancer cells in a SMAD ubiquitination regulatory factor 1 (SMURF1)-dependent manner and that SMURF1 induces degradation of ${\beta}-catenin$ in C2C12 cells. However, the relationship between EGF-induced SMURF1 and ${\beta}-catenin$ expression in breast cancer cells remains unclear. So, we investigated if EGF and SMURF1 regulate ${\beta}-catenin$ expression in MDAMB231 human breast cancer cells. When MDAMB231 cells were incubated with EGF for 24, 48, and 72 hours, EGF significantly increased expression levels of SMURF1 mRNA and protein while suppressing expression levels of ${\beta}-catenin$ mRNA and protein. Overexpression of SMURF1 downregulated ${\beta}-catenin$ mRNA and protein, whereas knockdown of SMURF1 increased ${\beta}-catenin$ expression and blocked EGF-induced ${\beta}-catenin$ downregulation. Knockdown of ${\beta}-catenin$ enhanced cell migration and invasion of MDAMB231 cells, while ${\beta}-catenin$ overexpression suppressed EGF-induced cell migration and invasion. Furthermore, knockdown of ${\beta}-catenin$ enhanced vimentin expression and decreased cytokeratin expression, whereas ${\beta}-catenin$ overexpression decreased vimentin expression and increased cytokeratin expression. These results suggest that EGF downregulates ${\beta}-catenin$ in a SMURF1-dependent manner and that ${\beta}-catenin$ downregulation contributes to EGF-induced cell migration and invasion in MDAMB breast cancer cells.