• The korean journal of orthodontics
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• v.25 no.1 s.48
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• pp.31-42
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• 1995

This study was designed to evaluate the expression of growth factor in periodontal tissue during the experimental movement of rat incisors by LSAB(Labelled streptavidine Biotin) immunohistochemical staining for EGF(Epidermal growth factor). 23 Sprague-Dawley rats were divided into a control group(3rats) and experimental groups(20rats), where a force(75g) from helical springs across the maxillary incisors was applied. Experimental groups were sacrificed at 12 hours, 1, 4, 7 and 14 days, after force application, respectively. And Tissue slides of control and experimental groups were studied immunohistochemically and histologically. The results were as follows : 1. In 14days after force application, periodontal fibers were strectched on the tension side, and compressed In pressure side of all experimental groups, and the arrangement of periodontal fibers was not recovered yet. 2. The degree of EGF expression in control group was strongly positive in the oral epithelium, predentin, capillaries in pulp and periodontal spaces. But osteoblasts and osteoclasts were stained mildly positive. 3. EGF expression was mild and diffuse in 12 hours, 1, 4 and 7 days of experimental groups and was not significantly different between the tension and pressure sides. 4. The degree of EGF expression in the 14-day experimental group was higher than any other group. And the tension side showed a more positive EGF expression than the pressure side. The apical area revealed a more positive EGF expression than the cervical area.

• Journal of Periodontal and Implant Science
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• v.26 no.2
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• pp.491-510
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• 1996

This study was performed to evaluate the effects of platelet-derived growth factor (PDGF) and epidermal growth factor (EGF) on the characteristics of beagle dog's periodontal ligament (BPD) cells and bone marrow (BBM) cells which have the important role on the early stage of periodontal tissue regeneration in vitro. In control group, the cells ($1.5{\times}10^5$cells/ml) were cultured alone with Dulbecco's Modified Eagle's Medium contained with 10% fetal bovine serum, $50{\mu]g/ml$ ascorbic acid, and 10mM/ml ${\beta}-glycerophosphate$. In experimental groups, growth factors, PDGF or EGF(10ng/ml), were added into the above culture condition. And then each group was characterized by examining the cell proliferation rate, amount of total protein synthesis, alkaline phosphatase activity at 1, 5, 9, 13, 17th day after seeding of cells into the culture wells. The results were as follows: 1. Both BPD and BBM cells in PDGF-treated group proliferated more rapidly than non-treated cells. This finding also was observed in EGF-treated group but it was not as prominent as that of PDGF-treated group. The proliferation rates of both cells showed the time-dependent pattern during experimental periods in all three groups. 2. Amount of total protein synthesis was more increased in PDGF-treated group than in control group. But no significant difference between EGF-treated group and control group was observed throughout experimental periods even though the tendency of amount of protein synthesis was time-dependent pattern. 3. Alkaline phosphatase activity also more increased in PDGF-treated group than control group. But slight decrease tendency was seen in both cells of EGF-treated group. From the above results, PDGF appeared to enhance the proliferation and cellular activities including amount of total protein synthesis and alkaline phosphatase activity of BPD and BBM cell, but EGF did not show notable effects. The optimal application of these growth factors was thought to be useful as the adjunctive means in periodontal regeneration procedures.

• 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.

• Journal of Chest Surgery
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• v.37 no.8
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• pp.691-701
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• 2004

Background: Tissue hypoxia is a characteristic of many human malignant neoplasms, and hypoxia inducible factor-1 (HIF-1) plays a pivotal role in essential adaptive response to hypoxia, and activates a signal pathway for the expression of the hypoxia-regulated genes, resulting in increased oxygen delivery or facilitating metabolic adaptation to hypoxia. Increased level of HIF-1 a has been reported in many human malignancies, but in esophageal squamous cell carcinoma, the influence of HIF-1 a on tumor biology, including neovascularization, is not still defined. Material and Method: The influence of HIF-1 a expression on angiogenic factors, correlation between the tumor proliferation and HIF-1 a expression, interaction of HIF-1 a expression and p53, and correlation between HIF-1 a expression and clinicopathological prognostic parameters were investigated, using immunohistochemical stains for HIF-1 a, VEGF, CD34, p53, and Ki-67 on 77 cases of resected esophageal squamous cell carcinoma. Result: HIF-1 a expression in cancer cells was found in 33 of 77 esophageal squamous cell carcinoma cases. The 33 cases (42.9%) showed positive stain for HIF-1 a. High HIF-1 a expression was significantly associated with several pathological parameters, such as histologic grade (p=0.032), pathological TMN stage (p=0.002), the depth of tumor invasion (p=0.022), regional lymph node metastasis (p=0.002), distant metastasis (p=0.049), and lymphatic invasion (p=0.004). High HIF-1 a expression had significant VEGF immunoreactivity (p=0.008) and Ki-67 labeling index (p<0.001), but was not correlated with microvascular density within tumors (p=0.088). The high HIF-1 a expression was correlated with aberrant p53 accumulation with a marginal significance (p=0.056). The overall 5-year survival rate was 34.9%. The survival rate of patients with a high HIF-1 a expression was worse than that of patients with low-expression tumors (log-rank test, p=0.0001). High HIF-1 a expression was independent unfavorable factors although statistical significance is marginal in multivariate analysis. Conclusion: It is suggested that (1) high HIF-1 a expression in esophageal squamous cell carcinoma is associated with tumor hypoxia, or with genetic alteration in early carcinogenesis and progressive stages, (2) high HIF-1 a expression may be associated with intratumoral neovascularization through HIF-VEGF pathway, and (3) high HIF-1 a expression is associated with poor prognosis in patients with esophageal squamous cell carcinoma and may playa role as biomarker for regional lymph node metastasis.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.35 no.5
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• pp.287-293
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• 2009

Cell survival is the result of a balance between programmed cell death and cellular proliferation. Cell membrane receptors and their associated signal transducing proteins control these processes. Of the numerous receptors and signaling proteins, epidermal growth factor receptor (EGFR) is one of the most important receptors involved in signaling pathways implicated in the proliferation and survival of cancer cells. EGFR is often highly expressed in human tumors including oral squamous cell carcinomas, and there is increasing evidence that high expression of EGFR is correlated with poor clinical outcome of common human cancers. Therefore, we examined the antiproliferative activity of gefitinib, epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI), in head and neck cancer cell lines. SCC-9, KB cells were cultured and growth inhibition activity of gefitinib was measured with MTT assay. To study influence of gefitinib in cell cycle, we performed cell cycle analysis with flow cytometry. Western blot was done to elucidate the expression of EGFR in cell lines and phosphorylation of EGFR and downstream kinase protein, Erk and Akt. Significant growth inhibition was observed in SCC-9 cells in contrast with KB cells. Also, flow cytometric analysis showed G1 phase arrest only in SCC-9 cells. In Western blot analysis for investigation of EGFR expression and downstream molecule phosphorylation, gefitinib suppressed phosphorylation of EGFR and downstream protein kinase Erk, Akt in SCC-9. However, in EGFR positive KB cells, weak expression of active form of Erk and Akt and no inhibitory activity of phosphorylation in Erk and Akt was observed. The antiproliferative activity of gefitinib was not correlated with EGFR expression and some possibility of phosphorylation of Erk and Akt as a predictive factor of gefitinib response was emerged. Further investigations on more reliable predictive factor indicating gefitinib response are awaited to be useful gefitinib treatment in head and neck cancer patients.

• The Korean Journal of Pesticide Science
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• v.5 no.4
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• pp.11-19
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• 2001

This review discusses the effects and roles of insect hormones and insect growth regulators (IGRs) on vitellogenesis in adult insects. Insect vitellogenesis is regulated by hormones such as juvenile hormone (JH), ecdysteroids, and neurosecretory hormones (ovaryecdysteroidogenic hormone : OEH) released by neurosecretory cells, diet, and other elements(male specific protein of sperm fluid). In the fat bodies, the vitellogenins are synthesized by the stimulation of JH released by corpus allatum (CA) and ecdysteroids produced by follicle cells with the ovary in most insects. Furthermore, vitellogenins are released into the hemolymph, transported to the ovarioles by carrier protein, and incorporated into oocytes for the developing ovary. Of IGRs, juvenile hormone and its mimics such as methoprene and pyriproxifen appear to have pharmacological effects such as membrane lysis, destruction of salivary grand and midgut epithlial cells, fat body cells, and ovarian tissue, and also anti-juvenile hormone such as precocenes I and II appear to have specific cytotoxicity such as inhibition of corpus allatum and oocytes development. These results suggest that IGRs may be useful as agents for integrated pest management.

• Tuberculosis and Respiratory Diseases
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• v.59 no.6
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• pp.631-637
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• 2005

Background : Transcriptional factors of the CREB(cAMP Response Element Binding Protein) are involved in the regulation of gene expression in response to a variety of signaling pathways. Proteins produced by the CREB genes play key roles in many physiological processes, including memory and long-term potentiation. The retinoic acid receptor (RAR) axis mediates epithelial cell differentiation and proliferation in many tissues including the lung. Material and method : The RAR and CREB expression levels were examined in 60 adenocarcinomas and 60 squamous cell carcinomas of the lung using immunohistochemical staining. Results : 1) RAR protein expression was found in 58.3%(35/60) of adenocarcinomas and 36.7%(22/60) of squamous cell carcinomas(P<0.05). 2) RAR protein expression was found in 80%(16/20) of well differentiated adenocarcinomas, 60%(12/20) of moderately differentiated adenocarcinomas, and 35%(7/20) of poorly differentiated adenocarcinomas (P<0.01). 3) RAR protein expression was found in 45%(9/20) of well differentiated squamous cell carcinomas, 35%(7/20) of moderately differentiated squamous cell carcinomas, and 30%(6/20) of poorly differentiated squamous cell carcinomas (P>0.05). 4) CREB expression was found in 61.7%(37/60) of adenocarcinomas and 40%(24/60) of squamous cell carcinomas( P<0.05). 5) CREB expression was found in 85%(17/20) of well differentiated adenocarcinomas, 60%(12/20) of moderately differentiated adenocarcinomas, and 40%(8/20) of poorly differentiated adenocarcinomas (P<0.01). 6) CREB expression was found in 45%(9/20) of well differentiated squamous cell carcinomas, 35%(7/20) of moderately differentiated squamous cell carcinomas, and 35%(8/20) of poorly differentiated squamous cell carcinomas(P>0.05). 7) RAR and CREB expression was found in 68.5% of lung cancers, and there was a significant correlation between them(P<0.05). Conclusion : RAR and CREB expression can be used to indirectly determine the malignant potentiality of a cell.

• Radiation Oncology Journal
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• v.14 no.4
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• pp.307-315
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• 1996

Purpose : The authors conducted a retrospective analysis of patients with the carcinoma of uterine cervix treated with curative radiation therapy to evaluate the prognostic factors that would affect the results of the therapy and to get the critical ideas in determining more aggressive treatment schedule. Methods and Materials : From January 1987 to December 1988. Four hundreds and sixty patients with uterine cervical carcinomas treated with radiotherapy at KCCH were registered to this retrospective study. One hundred and three patients were treated with external radiation therapy alone, and 357 patients were treated with external radiation followed by low dose rate intracavitary radiation therapy. The follow-up rate was 88% and median follow-up duration was 48 months. Results : The overall 5 year survival rate of the patients was 67.7%, and when classified by FIGO stages, 5 year survival rates were 81.2%, 76.3%, 73.1%, 50%. 52.3%, 11.5% for stages Ib, IIa, IIb, IIIa, IVa respectively. Tumor size(p=0.0002), endocervical growth pattern(p=0.003), lymph node invasion(p=0.0001), mean hemoglobin level(p=0.0001), and pathologic cell type(p=0.0001) were significant prognostic factors and decrease in survival for young age patient group was marginally important (p=0.03). Conclusion : Significant prognostic factors in the radiation therapy of the uterine cervical carcinoma were tumor size, growth pattern of tumor, lymph node invasion, pathologic cell type, hemoglobin level of patients during treatment and lower survival rate in young age group was obvious, too. Patients with large size tumor(${\geq)$4cm), especially combined with endocervical growth patterns or advanced stages(III or more) need more aggressive treatment to improve the outcome of treatment. And positive feature of lymph node invasion affected the result of therapy, so improvement in the diagnostic and therapeutic trial is essential.

• Tuberculosis and Respiratory Diseases
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• v.55 no.1
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• pp.21-30
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• 2003

Background : Mucin synthesis in airways has been reported to be regulated by the epidermal growth factor receptor (EGFR) system. Epidermal growth factor receptor transactivation was identified as a critical element in G-protein-coupled receptors (GPCRs)-induced mitogenic signaling. EGF receptor transactivation by G-protein-coupled receptors requires metalloproteinase cleavage of proHB-EGF. This study was hypothesized that lipopolysaccharide (LPS)-induced mucin production associates with epidermal growth factor receptor transactivation, and MUC5AC production associates with epidermal growth factor receptor transactivation by G-protein-coupled receptors that regulates by metalloproteinase. Method : MUC5AC mucin production was examined in NCI-H292 cells and MUC5AC protein synthesis was assessed using ELISA. For the evaluation of mechanism of LPS-induced MUC5AC production, $TNF{\alpha}$ was measured using ELISA with or without pretreatment of heterotrimeric G-protein inhibitor, mastoparan. MUC5AC protein was measure with pretreatment of polyclonal $TNF{\alpha}$ antibody or mastoparan on LPS-induced MUC5AC production. For the evaluation of relation of G-protein and MUC5AC production, G-protein stimulant, mastopara-7, or matrix metalloproteinase, ADAM10, was added to NCI-H292 cells. MUC5AC protein was measure with pretreatment of polyclonal EGF antibody on mastoparan-7-induced MUC5AC production. Results : LPS alone did not increase significantly MUC5AC production. LPS with $TNF{\alpha}$ induced dose-dependently MUC5AC production in NCI-H292 cells. LPS increased dose-dependently $TNF{\alpha}$ secretion, which was inhibited by mastoparan. LPS with $TNF{\alpha}$-induced MUC5AC production was inhibited by neutralizing polyclonal $TNF{\alpha}$ antibody, mastoparan or AG 1472. Mastoparan-7 or ADAM10 increased dose-dependently MUC5AC production, which was inhibited by polyclonal neutralizing EGF antibody. Conclusion : In LPS-induced MUC5AC synthesis, LPS causes $TNF{\alpha}$ secretion, which induces EGFR expression. EGFR tyrosine kinase phosphorylation result in MUC5AC production. EGF-R transactivation by G-protein-coupled receptors requires matrix metalloproteinase cleavage of proHB-EGF.

• Tuberculosis and Respiratory Diseases
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• v.54 no.1
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• pp.80-90
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• 2003

Background : Goblet cell hyperplasia is a critical pathological feature in hypersecretory diseases of the airways. A bacterial infection of the lung is also known to induce inflammatory responses, which can lead to the overproduction of mucus. Recently, mucin synthesis in the airways has been reported to be regulated by neutrophilic inflammation-induced epidermal growth factor receptor (EGFR) expression and activation. In addition, it was reported that migration of the activated neutrophils is dependent on the matrix metalloproteinases (MMPs), especially MMP-9. In this study, bacterial lipopolysaccharide (LPS)-induced goblet cell hyperplasia and mucus hypersecretion by EGFR cascade, resulting from the MMPs-dependent neutrophilic inflammation were investigated in the rat airways. Methods : Pathogen-free Sprague-Dawley rats were studied in vivo. Various concentrations of LPS were instilled into the trachea in $300{\mu}{\ell}$ PBS (LPS group). Sterile PBS ($300{\mu}{\ell}$) was instilled into the trachea of the control animals (control group). The airways were examined on different days after instilling LPS. For an examination of the relationship between the LPS-induced goblet cell hyperplasia and MMPs, the animals were pretreated 3 days prior to the LPS instillation and daily thereafter with the matrix metalloproteinase inhibitor (MMPI; 20 mg/Kg/day of CMT-3; Collagenex Pharmaceuticals, USA). The neutrophilic infiltration was quantified as a number in five high power fields (HPF). The alcian blue/periodic acid-Schiff (AB/PAS) stain were performed for the mucus glycoconjugates and the immunohistochemical stains were performed for MUC5AC, EGFR and MMP-9. Their expressions were quantified by an image analysis program and were expressed by the percentage of the total bronchial epithelial area. Results : The instillation of LPS induced AB/PAS and MUC5AC staining in the airway epithelium in a time- and dose-dependent manner. Treatment with the MMPI prevented the LPS-induced goblet cell hyperplasia significantly. The instillation of LPS into the trachea induced also EGFR expression in the airway epithelium. The control airway epithelium contained few leukocytes, but the intratracheal instillation of LPS resulted in a neutrophilic recruitment. A pretreatment with MMPI prevented neutrophilic recruitment, EGFR expression, and goblet cell hyperplasia in the LPS-instilled airway epithelium. Conclusion : Matrix metalloproteinase is involved in LPS-induced mucus hypersecretion, resulting from a neutrophilic inflammation and EGFR cascade. These results suggest a potential therapeutic role of MMPI in the treatment of mucus hypersecretion that were associated with a bacterial infection of the airways.