• Archives of Pharmacal Research
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• v.28 no.11
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• pp.1311-1316
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• 2005

To better define the relationship between dermal regeneration and wound contraction and scar formation, the effects of epidermal growth factor (EGF) loaded in collagen sponge matrix on the fibroblast cell proliferation rate and the dermal mechanical strength were investigated. Collagen sponges with acid-soluble fraction of pig skin were prepared and incorporated with EGF at 0, 4, and 8 $\mu$g/1.7 $cm^{2}$. Dermal fibroblasts were cultured to 80$\%$ confluence using DMEM, treated with the samples submerged, and the cell viability was estimated using MTT assay. A deep, $2^{nd}$ degree- burn of diameter 1 cm was prepared on the rabbit ear and the tested dressings were applied twice during the 15-day, post burn period. The processes of re-epithelialization and dermal regeneration were investigated until the complete wound closure day and histological analysis was performed with H-E staining. EGF increased the fibroblast cell proliferation rate. The histology showed well developed, weave-like collagen bundles and fibroblasts in EGF-treated wounds while open wounds showed irregular collagen bundles and impaired fibroblast growth. The breaking strength (944.1 $\pm$ 35.6 vs. 411.5 $\pm$ 57.0 Fmax, $gmm^{-2}$) and skin resilience (11.3 $\pm$ 1.4 vs. 6.5 $\pm$ 0.6 mJ/$mm^{2}$) were significantly increased with EGF­treated wounds as compared with open wounds, suggesting that EGF enhanced the dermal matrix formation and improved the wound mechanical strength. In conclusion, EGF-improved dermal matrix formation is related with a lower wound contraction rate. The impaired dermal regeneration observed in the open wounds could contribute to the formation of wound contraction and scar tissue development. An extraneous supply of EGF in the collagen dressing on deep, $2^{nd}$ degree-burns enhanced the dermal matrix formation.

• YAKHAK HOEJI
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• v.45 no.2
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• pp.190-204
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• 2001

This study was conducted to investigate for its effects on reproductive and developmental toxicity of recombinant human epidermal growth factor (rhEGF) in Sprague-Dawley rats. Male rats were administered rhEGF at doses of 1, 10, 100, and 1000$\mu$g/kg/day, respective1y, by subcutaneous injection from 63 days before and throughout to mating period until the day before sacrifice. Female rats were administered rhEGF at the same doses from 14 days before mating to day 20 of gestation or to day 21 of lactation. We examined the male and female fertility indices and maternal toxicity of F0 parental animals. Also, we examined the external, visceral, or skeletal malformation of fetuses, growth and development, behavior, and/or reproductive performance of F1 animals. At the highest dose (1,000 $\mu$g/kg), the mean body weights of F0 animals were significantly increased in males and females at 3 or 2 weeks after treatment, respective1y. No clinical signs and food intakes were observed at any time during the experimental period by rhEGF treatment. In autopsy examination, the relative and absolute liver weights significantly increased in both sexes of 1,000 $\mu$g/kg. At the highest dose (1,000 $\mu$g/kg), there was a statistically significant increase of pregnancy period and the number of dead fetuses. Moreover, significant increase of mean fetal body weight and decrease of number of live fetuses, which related to the difficult dilivery were observed in highest dose group. In Fl examination, no adverse effects on external, visceral, and skeletal malformation, physical and functional development, behavior or reproductive ability of Fl animals were observed in any group. Also, there was no significant difference between control and treated groups in copulation or fertility indices of Fl animals. These results indicate that rhEGF had no adverse effect on fertility and reproductive ability of Sprague-Dawley rats.

• Biomolecules & Therapeutics
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• v.4 no.2
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• pp.138-147
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• 1996

DWP401, a recombinant human epidermal growth factor, was subcutaneously administered to ICR mice at the dose levels of 0, 0.04, 0.2 and 1.0 mg/kg/day (15rats/sex/group) in order to evaluate the subchronic toxicity. General observations, examinations for food and water consumption, ophthalmoscopy and urinalysis were carried out during the study. For the complete gross and microscopic examinations, 10 mice/ sex/group were sacrificed at the ends of the dosing period, and the remaining animals were sacrificed with a 5 week recovery period. Examinations for hematology and blood biochemistry were also carried out at the time of recovery period. Based on the results, it was thought that the target tissue or organs were mesothelial cell, injection site, spleen, adrenal gland, ovary and transitional epithelial cell of urinary tract, and no observed toxic level of DWP401 was 0.04 mg/kg while definite toxic dose level might be 0.2 mg/kg.

• Molecules and Cells
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• v.20 no.2
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• pp.263-270
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• 2005

Transactivation of EGF-receptor (EGFR) by G-protein coupled receptors (GPCRs) is emerging as an important pathway in cell proliferation, which plays a crucial role in the development of atherosclerotic lesion. Angiotensin II (Ang II) has been identified to have a major role in the formation of atherosclerotic lesions, although the underlying mechanisms remain largely unclear. We hypothesize that Ang II promotes the proliferation and migration of smooth muscle cells through the release of heparin-binding epidermal growth factor like growth factor (HB-EGF), transactivation of EGFR and activation of Akt and Erk 1/2, with matrix metalloproteases (MMPs) playing a dispensable role. Primary rat aortic smooth muscle cells were used in this study. Smooth muscle cells rendered quiescent by serum deprivation for 12 h were treated with Ang II (100 nM) in the presence of either GM6001 ($20{\mu}M$), a specific inhibitor of MMPs or AG1478 ($10{\mu}M$), an inhibitor of EGFR. The levels of phosphorylation of EGFR, Akt and Erk 1/2 were assessed in the cell lysates. Inhibition of MMPs by GM6001 significantly attenuated Ang II-stimulated phosphorylation of EGFR, suggesting that MMPs may be involved in the transactivation of EGFR by Ang II receptor. Furthermore Ang II-stimulated proliferation and migration of smooth muscle cells were significantly blunted by inhibiting MMPs and EGFR and applying HB-EGF neutralization antibody, indicating that MMPs, HB-EGF and EGFR activation is necessary for Ang-II stimulated migration and proliferation of smooth muscle cells. Our results suggest that inhibition of MMPs may represent one of the strategies to counter the mitogenic and motogenic effects of Ang II on smooth muscle cells and thereby prevent the formation and development of atherosclerotic lesions.

• 대한생식의학회:학술대회논문집
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• 1995.12a
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• pp.58.1-58.1
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• 1995

• Journal of Chest Surgery
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• v.30 no.9
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• pp.854-861
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• 1997

CYPRA 21-1 is known to be a cytokeratin 19 fragment, and it can be detected by using two specific monoclonal antibodies (KS 19-1 and BM 19-21) and can be clinically applied as a useful circulating tumor marker The epidermal growth factor receptor (EGF-R) expression was evaluated and characterized by its tyrosine protein kinase activity and by its ligand-stimulated autophosphorylation, a property shared with other peptide growth factor receptors. Autocrine or para'urine action was initiated by a growth factor, or by a transforming growth factor o, which had an extensive homology with EGP and which also stimulated tyrosine kinase activity on the EGF-R. The CYFRA 21-1 and the EGF-R levels in 30 patients with primary lung tumors were investigated. There were 24 patients with squamous cell carcinomas and 6 patients with adenocarcinomas. Specimen 5 mm3 in size were sampled at three different locations ; the main lesion, the boundary between the lesion and the unaffected tissue, and the unaffected tissue of the patients. The results were as follows 1. The CYPRA 21-1 concentration in the cancer boundary, the most malignant region,(348.6 : 89.9 ng/ml) was the lowest value. The CYFRA 21-1 concentration in unaffected tissue,(718.4$\pm$77.8 ng/ml) was higher than that in the main lesion. which had intact cellularity. 2. The EGF-R concentration in the main lesion was higher than that in the unaffected tissue, and the EGF-R concentration in a squamous cell cacinoma was higher than that in an adenocarcinoma. also, the EGF-R concentration in the cancer b undary was highest at stage 1, ll. The EGF-R concentration was higher in the main cancer lesion that in the unaffected tissue at stage 111, IV. 3. The CYFRA 21-1 was a cytoplasmic skeleton and the EGF-R was a cell-wall component; there was no correlation. In conclusion, CYFRA 21-1 was abundant in the cytoplasm but had a higher concentration in the unaffected tissue than in the main cancer lesion. The CYFRA 21-1 concentration of the tissue did not reflect the amount of cancer activity, the EGP-R was located in the cell membrane, the level of tissue that reflects cancer activity, so the main cancer lesion had a higher concentration than the unaffected tissue. CYFRA 21-1 is not a useful tumor maker at the tissue level. Because the EGF-R concentration re(looted the cancer activity, its a useful tumor marker for lung cancer.

• Journal of the Korean Society of Food Science and Nutrition
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• v.23 no.2
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• pp.340-347
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• 1994

The specimens used in this study were obtained from patients with primary gastric carcinoma and adjacent non-malignant mucosa from the same patients. Using the techniques of immunocyto chemicstry and in situ hybridization, transforming growth $factor-{\alpha}(TGF-{\alpha})$ and epiderimal growth factor receptor (EGF-R) nRNAs were identified. $TGF-{\alpha}$ was observed in macrophages and dividing tumor cells but, not in normal cells. EGF-R was observed both in malignant and non-malignant gastric tissues. Although normally, $TGF-{\alpha}$ is not seen in normal gastric tissues, $TGF-{\alpha}$ was discovered in the adjacent non-malignant tissue of histolgically normal, which strongly suggest that $TGF-{\alpha}$ is involved in the differentiation of cancer cells. Immunocytochemicstry using EMB-11 antibody identified the existence of macrophages which express $TGF-{\alpha}$ and EGF-R mRNA. Protein products of EGF-R was identfified using monoclonal antibody. Cancer cells were also identified in the non-malignant normal tissues by the method of immunocytochemicstry using carcino embryonic antigen (CEA)antibody. It is considered that the activity of $TGF-{\alpha}$ increased as tumor cell prolifierates. Immunocytochemistry and in situ hybridization techniques can be used to diagnose gastric cancer along with the use of ${\alpha}-feto$ protein and CEA.

• Imaging Science in Dentistry
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• v.30 no.1
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• pp.71-79
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• 2000

Purpose : This study was aimed to evaluate the cell cycle arrest and apoptosis induction after irradiation and epidermal growth factor (EGF) treatment in three human epithelial tumor cell lines (A431, Siha, KB). Materials and Methods: Single irradiation of 2, 5 and 10 Gy was done on three cell lines with 5.38 Gy/min dose rate using Cs-137 irradiator at room temperature. Also, EGF of 10 ng/ml was added immediately after 10 Gy irradiation. Cell growth was evaluated by counting the living cell number using a hemocytometer at 1 day, 2 days, 3 days, 4 days and 5 days after irradiation. Cell cycle arrest and apoptosis induction were assayed with the flow cytometry at 8 hours, 12 hours, 1 day, 2 days, 3 days, 4 days and 5 days after irradiation. Results : Growth of irradiated three cell lines were inhibited in proportion to radiation dose. EGF treatment after irradiation showed various results according to cell lines. On all cell lines, G2 arrest was detected after 8 hours and maximized after 12 hours or 1 day. Amount of G2 arrest was positively dose dependent. However, EGF showed no significant change on G2 arrest. G2 arrest was recovered with time at 2 Gy and 5 Gy irradiation. However, at 10 Gy irradiation, G2 arrest was continued. Apoptosis was detected at 10 Gy irradiation. On EGF treated group after irradiation, A431 and Siha cell lines showed slightly increased apoptosis but there was no statistically significant difference. KB cell line showed no marked change of apoptosis induction. Conclusion : Irradiation effects on cell cycle arrest and apoptosis induction in three human epithelial tumor cell lines, however epidermal growth factor doesn't effect on.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.8
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• pp.4859-4864
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• 2013

Background: The purpose of this study was to assess the effectiveness of a recombinant human epidermal growth factor (EGF)-based cream for the prevention of acute radiation dermatitis in breast cancer patients receiving radiotherapy (RT). Materials and Methods: Between December 2012 and April 2013, 40 breast cancer patients who received postoperative RT were prospectively enrolled in this study and randomly assigned to receive human recombinant EGF-based cream (intervention group) or general supportive skin care (control group). The grade of radiation dermatitis and pain score were examined at weekly intervals during RT and 6 weeks after RT completion. Results: All patients completed the planned RT and complied well with instructions for applying the study cream and general supportive skin care. In the intervention group, radiation dermatitis of maximum grade 3, 2, and 1 developed in 3 (15%), 11 (55%), and 6 patients (30%), respectively. In comparison, in the control group, radiation dermatitis of maximum grade 3, 2, and 1 developed in 8 (40%), 10 (50%), and 2 patients (10%), respectively. The intervention group showed lower incidence of grade 3 radiation dermatitis than the control group (p=0.068 in univariate analysis and p=0.035 in multivariate analysis). There was no statistically significant difference in the maximal pain score between the two groups (p=0.934). Conclusions: This single-blind randomized preliminary study showed that recombinant human EGF-based cream can have a beneficial role in preventing or minimizing radiation dermatitis in breast cancer patients. To confirm the results of our study, additional studies with a large sample size are required.

• Archives of Plastic Surgery
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• v.41 no.5
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• pp.466-471
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• 2014

Background Bleeding can be a problem in wound debridement. In search for an effective hemostatic agent, we experimented with a chitosan film combined with the recombinant human epidermal growth factor (rh-EGF), hypothesizing that it would achieve effective hemostasis and simultaneously enhance arterial healing. Methods Forty-eight Sprague-Dawley rats were used, and 96 puncture wounds were made. The wounds were divided into the following four groups: treated with sterile gauze, treated with gelatin sponge, treated with chitosan, and treated with chitosan combined with rh-EGF. Immediate hemostasis was evaluated, and arterial healing was observed histologically. Results Groups B, C, and D showed a significant rate of immediate hemostasis as compared to group A (P<0.05), but there were no significant differences among groups B, C, and D. Histologically, only group D showed good continuity of the vessel wall after 1 week. It was the only group to show smooth muscle cell nuclei of the vessel wall. Conclusions We observed that chitosan has an effective hemostatic potential and the mix of rh-EGF and chitosan does not interfere with chitosan's hemostatic capabilities. We also identified enhanced healing of vessel walls when rh-EGF was added to chitosan. Further research based on these positive findings is needed to evaluate the potential use of this combination on difficult wounds like chronic diabetic ulcerations.