• Radiation Oncology Journal
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• v.24 no.3
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• pp.179-184
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• 2006

[ $\underline{Purpose}$ ]: To explore the effect of recombinant human EGF on the proliferation and survival of human fibroblast cell lines following irradiation. $\underline{Materials\;and\;Methods}$: Fibroblast was originated human skin and primary cultured. The trypan blue stain assay and MTT assay were used to study the proliferative effects of EGF on human fibroblast cell lines in vitro. An incubation of fibroblasts with rhEGF for 24 hours immediately after irradiation was counted everyday. Cell cycle distributions were analyzed by FACS analysis. $\underline{Results}$: Number of fibroblast was significantly more increased rhEGF (1.0 nM, 10 nM, 100 nM, 1,000 nM) treated cell than control after 8 Gy irradiation. Most effective dose of rhEGF was at 160 nM. These survival differences were maintained at 1 week later. Proportion of S phase was significantly increased on rhEGF treated cells. $\underline{Conclusion}$: rhEGF cause increased fibroblast proliferation following irradiation. We expect that rhEGF was effective for radiation induced wound healing.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.34 no.3
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• pp.245-249
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• 2008

Epidermal growth factor is a single-chain polypeptide consisting of 53 amino acids and has a potent mitogenic activity that stimulates proliferation of various normal and neoplastic cells through the interaction with its specific receptor(epidermal growth factor receptor, EGFR). Pleomorphic adenoma is the most common salivary benign tumor and histologically, it contains the epithelial cell, the myo-epithelial cell and mesenchymal ingredient, which is various aspect. Adenoid cystic carcinoma is an infiltrative malignant salivary gland tumor with three different histological patterns: cribriform, tubular or solid. The tumor cell structure composed of modified myoepithelial cell, and basaloid cell. In this study, we used an immunohistochemical technique to investigate the expression of EGF in 6 specimens of adenoid cystic carcinoma and 10 specimens of pleomorphic adenoma taken from patients treated at Dept. of Oral and Maxillofacial Surgery, Dankook University. The results were as follows. 1. In pleomorphic adenoma, ductal structure and scattered spindle cells in hyalinized stroma, disclosing myxoid stroma and hyalin, cartilage formation were observed. Immunohistologically, weak EGF expression in ductal structure and negative in stromal area were observed. 2. Cribriform type of adenoid cystic carcinoma showed numerous pseudocyst surrounded by dark small neoplastic cells in the back-ground of fibrous connective tissue and moderate EGF expression of dark cells adjacent to pseudo lumen in cribriform pattern, while weak expression in other most cells. 3. Tubular type of adenoid cystic carcinoma showed numerous ductal pattern surrounded by two layered neoplastic cells in the back-ground of fibrous connective tissue and strong EGF expression in luminal cells of ductal structure, while weak expression in outer cells. From the results obtained, we suggest that EGF is mainly biosynthesized in cells forming duct like structures of tubulo-ductal type or cribriform adenoid cystic carcinoma and it may play a role, as a cell mitogen in adenoid cystic carcinoma growth.

• Korean Journal of Clinical Laboratory Science
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• v.49 no.2
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• pp.150-160
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• 2017

Atopic dermatitis (AD) is a chronic inflammatory skin disease. It is characterized by eczematous lesions, skin dryness, and pruritus. The existing treatment drugs for AD have side effects, especially if the drugs are taken for extended periods. Therefore, new alternative therapies are necessary. The aim of this study was to investigate the combined effects of curcumin administration and LED irradiation on AD. AD-like lesions were induced in BALB/c mice by repeated application of 1-chloro-2,4-dinitrobenzene (DNCB) to the shaved skin of the ear and neck. Thirty male BALB/c mice were divided into five groups: vehicle, DNCB, curcumin, LED, and curcumin+LED groups. Curcumin (0.1 g/kg/day) was administrated repeatedly during a period of 14 days (experimental period) and 630 nm LED irradiation ($5J/cm^2/day$) was performed in the acryl box once a day for 10 days, after inducing AD-like lesions via DNCB application. The severity of AD-like lesions was evaluated during the experimental period, using a modified SCORAD index. Both ear and neck skin tissues were examined histologically for epidermal thickness, mast cell, eosinophil counting, and dermal collagen density. Epidermal cell proliferation and apoptosis were detected using immunohistochemistry and TUNEL, respectively. These were all reduced in SCORAD index, epidermal thickness, collagen density, number of mast cell and eosinophil in dermis, and number of proliferating cell and apoptotic cell in epidermis by curcumin administration and 630 nm LED irradiation. Moreover, all parameters were significantly lower in the curcumin+LED group compared with the curcumin group and LED group. These results suggest that the combined therapy of curcumin and LED is more effective than a single treatment. We recommend that this can be a feasible alternative therapy to manage AD.

• Journal of Life Science
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• v.17 no.2 s.82
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• pp.185-191
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• 2007

Akt/PKB plays pivotal roles in many physiological responses such as proliferation, differentiation, apoptosis, and angiogenesis. Here we show that tyrosine phosphorylation of Akt/PKB is essential for the subsequent phosphorylation at $Thr^{\308}$. Tyrosine phosphorylation of Akt/PKB was induced by stimulation of COS-7 cells with epidermal growth factor receptor (EGF) and its phosphorylation was significantly enhanced by constitutive targeting of Akt/PKB to the plasma membrane by myristoylation. Interestingly, incubation of affinity purified Myc-tagged Akt/PKB with purified EGF receptor resulted in tyrosine phosphorylation as well as $Ser^{\473}$ phosphorylation of Akt/PKB. In addition, tyrosine-phosphorylated Akt/PKB could directly associate with activated EGF receptor in vitro. Finally, alanine mutation at putative tyrosine phosphorylation site $(Tyr^{\326})$ abolished EGF induced $Thr^{\308}$ phosphorylation of wild type as well as constitutively active form of Akt/PKB. Given these results we suggest here that direct tyrosine phosphorylation of Akt/PKB by EGF receptor could be another mechanism of EGF-induced control of many physiological responses.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.6
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• pp.2753-2758
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• 2014

Background: GC-binding factor 2 (GCF2) is a transcriptional regulator that represses transcriptional activity of the epidermal growth factor receptor (EGFR) by binding to a specific GC-rich sequence in the EGFR gene promoter. In addition to this function, GCF2 has also been identified as a tumor-associated antigen and regarded as a potentially valuable serum biomarker for early human hepatocellular carcinoma (HCC) diagnosis. GCF2 is high expressed in most HCC tissues and cell lines including HepG2. This study focused on the influence of GCF2 on cell proliferation and apoptosis in HepG2 cells. Materials and Methods: GCF2 expression at both mRNA and protein levels in HepG2 cells was detected with reverse transcription (RT) PCR and Western blotting, respectively. RNA interference (RNAi) technology was used to knock down GCF2 mRNA and protein expression. Afterwards, cell viability was analyzed with a Cell Counting Kit-8 (CCK-8), and cell apoptosis and caspase 3 activity by flow cytometry and with a Caspase 3 Activity Kit, respectively. Results: Specific down-regulation of GCF2 expression caused cell growth inhibition, and increased apoptosis and caspase 3 activity in HepG2 cells. Conclusions: These primary results suggest that GCF2 may influence cell proliferation and apoptosis in HepG2 cells, and also provides a molecular basis for further investigation into the possible mechanism at proliferation and apoptosis in HCC.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.4
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• pp.493-501
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• 1998

The most significant direct role of estrogen in vivo is its ability to elicit receptor-mediated cellular proliferation in mammalian target tissues. However, the mechanism by which exogenously added estrogen causes the neoplastic transformation of renal cortical cells is yet to be uncovered. The present study was designed to evaluate interaction of $17{\beta}-estradiol\;(E_2)$ with epidermal growth factor (EGF) and insulin-like growth factor-I (IGF-I) on proliferation and $P_i$ uptake in primary cultured rabbit renal proximal tubular cells in phenol red-free, hormonally defined-medium. $[^3H]-thymidine$ incorporation increased markedly by about 133% and 141% more in the presence of $10^{-9}\;and\;10^{-6}\;M\;E_2$, respectively, than that of control. Cell count was 162% and 143% greater in the presence of $10^{-9}\;and\;10^{-6}\;M\;E_2$ , respectively, compared with control. Among all time points examined, there was an increase in $[^3H]-thymidine$ incorporation in the presence of $10^{-9}\;M\;E_2$ at day 9 or 13, respectively. However, $E_2$ ($10^{-9}\;M$) significantly drove up cell count to 160% of that of control at day 13, while it had a slight but statistically insignificant effect at day 9. $E_2-induced$ stimulation of $[^3H]-thymidine$ incorporation was completely reversed by $E_2$ antagonists (progesterone or tamoxifen). $E_2$ ($10^{-9}\;M$) or EGF ($10^{-8}\;M$) significantly stimulated $[^3H]-thymidine$ incorporation by 144% and 154% of control. $E_2$ plus EGF was synergistic on $[^3H]-thymidine$ incorporation (204% of control), while $E_2$ plus IGF-I showed a slight but no significant synergistic effect. Cell number also displayed similar pattern. $E_2$ ($10^{-9}\;M$) significantly stimulated $P_i$ uptake to 134% of control. $E_2$-induced stimulation of $P_i$ uptake was partially reversed by $E_2$ antagonists. EGF or IGF-I ($10^{-8}\;M$) significantly also increased $P_i$ uptake to 132% or 129% of control. $E_2$ plus EGF had synergistic effect on $P_i$ uptake, while $E_2$ plus IGF-I did not. In conclusion, $E_2$ may act not only directly interaction with its receptors but also indirectly as a modulator of EGF in proliferation and $P_i$ uptake of primary cultured rabbit renal proximal tubular cells.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.33 no.3
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• pp.1-26
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• 2020

Objectives : This study was to examine the effects of 3 types of BTS which were excluded talcum only or replaced talcum to Lonicera japonicae Flos or Kochiae Fructus on the DNCB-induced atopic dermatitis in mice. Methods : In this study, Balb/c mice were divided into five groups: normal, control, GBT(BTS except talcum), GBTG(GBT added Lonicera japonicae Flos), and GBTJ(GBT added Kochiae Fructus). And the effects on atopic dermatitis were evaluated by weight change, ear's thickness and weight, thickness of dorsal skin, severity scale of dorsal skin, histopathologic findings of dorsal skin by H&E and toluidine blue stain, proliferation of splenocyte and thymocyte in vitro, proliferation of splenocyte in vivo, IL-4, TNF-α, IgE in serum. Results : There were no significantly changes in body weight and effect of ear's weight in GBT, GBTG, and GBTJ group. The thickness of ear of GBT and GBTJ group showed significant decrease. And the thickness of dorsal skin of GBTJ group significantly decreased compared to the control, GBT, and GBTG group. All the treated groups significantly decreased in severity scale, histopathologically reduced epidermal thickness, and mast cell infiltration. In vitro, all the treated groups increased in the proliferation rates of splenocyte. However, in vivo study, it showed a falling tendency and GBT group significantly decreased compared to control, GBTG, and GBTJ group. In vitro study, GBTG group significantly decreased in the proliferation rates of thymocyte. There was no IgE contents chnage in GBT, GBTG, and GBTJ groups but IL-4 and TNF-α contents were significantly decreased. Conclusions : GBT, GBTG, and GBTJ are expected to improve symptoms of atopic dermatitis and further studies are needed for development of BTS's transformation.

• Journal of Haehwa Medicine
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• v.28 no.2
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• pp.41-47
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• 2019

Objectives : Atopic dermatitis is an irritable skin disease accompanying rash and itching leading to impaired skin barrier. ATO-ALL is an ethanol extract of natural products comprising 12 herbs and effective on atopic dermatitis. In this study, we aimed to propose that the effect of ATO-ALL on skin regeneration in human keratinocyte cell line, HaCaT cells. Methods : To evaluate the skin regenerating effects of ATO-ALL, scratch wound healing assay, bromodeoxyuridine (BrdU) assay, and propidum iodide (PI) assay were performed using cultured HaCaT cell line. Result : Scratch wound healing assay showed that ATO-ALL was able to enhance the gap filling activity more than 2-fold at 7 ppm concentration compared with control group. BrdU assay demonstrated that ATO-ALL treatment increased the de novo cell proliferation in a dose-dependent manner. Finally, PI assay indicated that the cell cycle of HaCaT cells was modulated by ATO-ALL treatment. Conclusions : These results suggested that ATO-ALL may have skin regenerating effects by increasing cell proliferation via cell cycle regulation. Taken together, ATO-ALL is supposed to have a potential on regeneration of damaged skin or functional disease including atopic dermatitis.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4751-4756
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• 2012

Colon cancer continues to be one of the most common cancers, and the importance and necessity of new therapies needs to be stressed. The most important proto-oncogen factors for colon cancer appear to be epidermal growth factor receptor, EGFR, and c-Src with high expression and activity leading to tumor growth and ultimately to colon cancer progression. Application of c-Src and EGFR antisense agents simultaneously should theoretically therefore have major benefit. In the present study, anti-EGFR and c-Src specific antisense oligodeoxynucleotides were combined in a formulation using PAMAM dendrimers as a carrier. Nano drug entry into cells was confirmed by flow cytometry and fluorescence microscopy imaging and real time PCR showed gene expression of c-Src and EGFR, as well as downstream STAT5 and MAPK-1 with the tumor suppressor gene P53 to all be downregulated. EGFR and c-Src protein expression was also reduced when assessed by western blotting techniques. The effect of the antisense oligonucleotide on HT29 cell proliferation was determined by MTT assay, reduction beijng observed after 48 hours. In summary, nano-drug, anti-EGFR and c-Src specific antisense oligodeoxynucleotides were effectively transferred into HT-29 cells and inhibited gene expression in target cells. Based on the results of this study it appears that the use of antisense EGFR and c-Src simultaneously might have a significant effect on colon cancer growth by down regulation of EGFR and its downstream genes.

• Applied Microscopy
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• v.28 no.3
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• pp.307-314
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• 1998

The author has undertaken this study for demonstrating the relationship between keratinization and proliferation as well as remodeling of epidermis. Healthy ICR strain male mice, weighing about $20\sim25gm$, were used as experimental animals. Under the general anesthesia with ether the skins of experimental animals were subjected to a dorsal, transverse, full-thickness incision with 0.5cm in length, and removed them on 3rd day, 7th day and 2nd week after operation Specimens were prepared for electron microscopic study. The results obtained were as follows: The epidermis of 3rd day group is made up of $7\sim8$ keratinocytes. The new epidermal cells are grown beneath the necrotic tissue. Keratohyaline granules (KHGs) are visible in some granular cells. Various sited-KHGs are seen in granular layer cell, and in spinous cell ribosomes, tonofilaments and lamellar granules are seen. The epidermis of 7th day group is made up of $7\sim8$ keratinocytes. Numerous KHGs are seen in granular layer cells. KHGs are located in granular layer cells as well as spinous layer cells. The epidermis of End week group is composed of one-layered basal cell and $1\sim2$ layered superficial cells. Various sized-KHGs are observed in granular layer cells. The results of the present study suggest that as the epidermis should be keratinized during proliferation and remodeling process, so keratinization of the epidermis would play a major role of wound healing process.