• Microbiology and Biotechnology Letters
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• v.24 no.5
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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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• v.34 no.2
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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.

• Proceedings of the PSK Conference
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• 2001.04a
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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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• v.26 no.2
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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.

• Proceedings of the Korean Society of Embryo Transfer Conference
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• 2002.11a
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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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• v.18 no.4
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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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• v.28 no.8
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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.

• Journal of Life Science
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• v.18 no.2
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• pp.279-283
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• 2008

A 12.6-year-old, male Shitzu was diagnosed with perianal adenocarcinoma. The presented mass was brown to black, $4{\times}3{\times}3cm$ in size, and yellowish on cut section. Microscopic findings revealed that the mass composed of variable sized clusters of hepatoid cells with inconspicuous distinct. The tumor cells were polyhedral and pyknotic and exhibited high mitotic activity. Tumor cells intermingled with basaloid cells and primitive cells invaded the adjacent normal tissues. Basaloid cells exhibited positive immunoreactivity for Epidermal growth factor receptor (EGFR), human epidermal growth factor receptor (HER-2/neu), matrix metallopnateinase 9 (MMP-9), and perianal adenocarcinoma, protein kinase C alpha (PKC ${\alpha}$). Generally, tumors of the perianal gland are common and benign 4.5 times more often than carcinoma in the dog, particularly in males. In the present report, we examined histopathological and immunohistochemical characteristics of a rare perianal adenocarcinoma in association with proteins involved tumor metastasis and adenocarcinoma development.

• Radiation Oncology Journal
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• v.24 no.1
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• pp.67-76
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• 2006

Purpose: Oral mucositis is a common toxicity of radiation or chemotherapy, which is used a treatment for head and neck cancer. We investigated effects of recombinant human epidermal growth factor (rhEGF) on radiation-induced oral mucositis in rat model. Materials and Methods: Spraque-Dawley rats (7 per group) exposed to a single dose of 25 Gy (day 0) on their head, except for one group, were randomly divided into un-treated, vehicle-treated, and two rhEGF-treated groups. Rats were topically applied with rhEGF (15 or $30{\mu}g/oral$ cavity/day) or vehicle to their oral mucosa. Survival rate of rats, weight changes, and food intakes were examined from day 0 to 18 after radiation. Histology study was performed from oral mucosa of rats at day 7 and 18 after radiation. Results: rhEGF-treated groups (15 or $30{\mu}g/oral$) showed all survival rate 33%, whereas un-treated and vehicle-treated groups showed all survival rate 0% at the end of experiment. rhEGF-treated groups statistically had less weight loss compared to vehicle-treated group from day 2 to 7 after radiation. Food intake of rats with rhEGF treatment turned to increase at day 14 after radiation. At 7 day after radiation, un-treated and vehicle-treated groups showed severe pseudomembraneous or ulcerative oral mucositis. On the other hand, rhEGF-treated groups had no more than cellular swelling and degeneration of epidermal cells in oral mucosa of rats. Conclusion: These results suggest that rhEGF has significantly positive effects on radiation-induced oral mucositis in rats. rhEGF display a therapeutic potential on a clinical level.

• International Journal of Oral Biology
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• v.43 no.3
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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.