• Radiation Oncology Journal
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• v.25 no.4
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• pp.242-248
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• 2007

Purpose: To study the effect of recombinant human epidermal growth factor (rhEGF) on oral mucositis induced by cisplatin and radiotherapy in a mouse model. Materials and Methods: Twenty-four ICR mice were divided into three groups-the normal control group, the no rhEGF group (treatment with cisplatin and radiation) and the rhEGF group (treatment with cisplatin, radiation and rhEGF). A model of mucositis induced by cisplatin and radiotherapy was established by injecting mice with cisplatin (10 mg/kg) on day 1 and with radiation exposure (5 Gy/day) to the head and neck on days $1{\sim}5$. rhEGF was administered subcutaneously on days -1 to 0 (1 mg/kg/day) and on days 3 to 5 (1 mg/kg/day). Evaluation included body weight, oral intake, and histology. Results: For the comparison of the change of body weight between the rhEGF group and the no rhEGF group, a statistically significant difference was observed in the rhEGF group for the 5 days after day 3 of. the experiment. The rhEGF group and no rhEGF group had reduced food intake until day 5 of the experiment, and then the mice demonstrated increased food intake after day 13 of the of experiment. When the histological examination was conducted on day 7 after treatment with cisplatin and radiation, the rhEGF group showed a focal cellular reaction in the epidermal layer of the mucosa, while the no rhEGF group did not show inflammation of the oral mucosa. Conclusion: These findings suggest that rhEGF has a potential to reduce the oral mucositis burden in mice after treatment with cisplatin and radiation. The optimal dose, number and timing of the administration of rhEGF require further investigation.

• Parasites, Hosts and Diseases
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• v.55 no.5
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• pp.491-503
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• 2017

The effects of tyrosine kinase inhibitors (TKIs) were evaluated on growth inhibition of intracellular Toxoplasma gondii in host ARPE-19 cells. The number of tachyzoites per parasitophorous vacuolar membrane (PVM) was counted after treatment with TKIs. T. gondii protein expression was assessed by western blot. Immunofluorescence assay was performed using Programmed Cell Death 4 (PDCD4) and T. gondii GRA3 antibodies. The TKIs were divided into 3 groups; non-epidermal growth factor receptor (non-EGFR), anti-human EGFR 2 (anti-HER2), and anti-HER2/4 TKIs, respectively. Group I TKIs (nintedanib, AZD9291, and sunitinib) were unable to inhibit proliferation without destroying host cells. Group II TKIs (lapatinib, gefitinib, erlotinib, and AG1478) inhibited proliferation up to 98% equivalent to control pyrimethamine ($5{\mu}M$) at $20{\mu}M$ and higher, without affecting host cells. Group III TKIs (neratinib, dacomitinib, afatinib, and pelitinib) inhibited proliferation up to 98% equivalent to pyrimethamine at $1-5{\mu}M$, but host cells were destroyed at $10-20{\mu}M$. In Group I, TgHSP90 and SAG1 inhibitions were weak, and GRA3 expression was moderately inhibited. In Group II, TgHSP90 and SAG1 expressions seemed to be slightly enhanced, while GRA3 showed none to mild inhibition; however, AG1478 inhibited all proteins moderately. Protein expression was blocked in Group III, comparable to pyrimethamine. PDCD4 and GRA3 were well localized inside the nuclei in Group I, mildly disrupted in Group II, and were completely disrupted in Group III. This study suggests the possibility of a vital T. gondii TK having potential HER2/4 properties, thus anti-HER2/4 TKIs may inhibit intracellular parasite proliferation with minimal adverse effects on host cells.

• Biomolecules & Therapeutics
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• v.29 no.3
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• pp.303-310
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• 2021

In the present study, kaempferol, a flavonoidal natural compound found in Polygonati Rhizoma, was investigated for its potential effect on the gene expression and production of airway MUC5AC mucin. A human respiratory epithelial NCI-H292 cells was pretreated with kaempferol for 30 min and stimulated with epidermal growth factor (EGF) or phorbol 12-myristate 13-acetate (PMA), for the following 24 h. The effect on PMA-induced nuclear factor kappa B (NF-κB) signaling pathway or EGF-induced mitogen-activated protein kinase (MAPK) signaling pathway was investigated. Kaempferol suppressed the production and gene expression of MUC5AC mucins, induced by PMA through the inhibition of degradation of inhibitory kappa Bα (IκBα), and NF-κB p65 nuclear translocation. Also, kaempferol inhibited EGF-induced gene expression and production of MUC5AC mucin through regulating the phosphorylation of EGFR, phosphorylation of p38 MAPK and extracellular signal-regulated kinase (ERK) 1/2 (p44/42), and the nuclear expression of specificity protein-1 (Sp1). These results suggest kaempferol regulates the gene expression and production of mucin through regulation of NF-κB and MAPK signaling pathways, in human airway epithelial cells.

• Journal of Gastric Cancer
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• v.14 no.3
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• pp.180-186
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• 2014

Purpose: At present, a human epidermal growth factor receptor 2 (HER2)-based concept of tumor biology has been established, and trastuzumab ($Herceptin^{(R)}$; Genentech/Roche, San Francisco, CA, USA), a monoclonal humanized antibody directed against HER2, is a pivotal agent for the management of HER2 positive (HER2+) metastatic breast cancer. It is also known that HER2 has a predictive value in gastric cancer; however, its association with the prognosis of this disease remains uncertain. The purpose of this study was to evaluate both the relationship between HER2 overexpression in the tumors of gastric cancer patients, and the prognosis of these patients who have had curative resection. Materials and Methods: A total of 139 consecutive patients with gastric cancer who underwent surgery at the Kosin University Gospel Hospital between October 2011 and March 2012 were included in this retrospective study. All tumor samples were examined for HER2 expression by immunohistochemistry. A retrospective review of the medical records was conducted to determine the correlation between the presence of HER2 overexpression and clinicopathological factors. Results: The HER2+ rate was 15.1%. HER2 overexpression was associated with histological grade (P=0.044) and Lauren classification (P=0.036). There was no significant difference in the 2-year overall survival between HER2+ and HER2- patients (P=0.396). Multivariate analysis showed that HER2 was not an independent prognostic factor. Conclusions: HER2 overexpression in tumors was associated with histological grade and Lauren classification in gastric cancer patients with curative resection. However, HER2 was not an independent prognostic factor for gastric cancer in our study.

• Natural Product Sciences
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• v.25 no.3
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• pp.248-254
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• 2019

In the present study, we investigated whether quercitrin, quercetin and afzelin derived from Houttuynia cordata affect the production and gene expression of MUC5AC mucin from airway epithelial cells. Confluent NCI-H292 cells were pretreated with quercitrin, quercetin or afzelin for 30 min and then stimulated with epidermal growth factor (EGF) or phorbol 12-myristate 13-acetate (PMA) for 24 h. The MUC5AC mucin gene expression and production were measured by RT-PCR and ELISA, respectively. The results were as follows: (1) Quercitrin, quercetin and afzelin inhibited EGF- and PMA-induced MUC5AC mucin production from NCI-H292 cells; (2) The three natural products also decreased EGF- and PMA-induced MUC5AC mucin gene expression in NCI-H292 cells. These results suggest that quercitrin, quercetin and afzelin showed the regulatory effect on the steps of gene expression and production of mucin, by directly acting on airway epithelial cells.

• Journal of Gastric Cancer
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• v.24 no.1
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• pp.29-56
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• 2024

In recent years, remarkable progress has been made in the molecular profiling of gastric cancer. This progress has led to the development of various molecular classifications to uncover subtype-specific dependencies that can be targeted for therapeutic interventions. Human epidermal growth factor receptor 2 (HER2) is a crucial biomarker for advanced gastric cancer. The recent promising results of novel approaches, including combination therapies or newer potent agents such as antibody-drug conjugates, have once again brought attention to anti-HER2 targeted treatments. In HER2-negative diseases, the combination of cytotoxic chemotherapy and programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitors has become the established standard of care in first-line settings. In the context of gastric cancer, potential biomarkers such as PD-L1 expression, Epstein-Barr virus, microsatellite instability, and tumor mutational burden are being considered for immunotherapy. Recently, promising results have been reported in studies on anti-Claudin18.2 and fibroblast growth factor receptor 2 treatments. Currently, many ongoing trials are aimed at identifying potential targets using novel approaches. Further investigations will be conducted to enhance the progress of these therapies, addressing challenges such as primary and acquired resistance, tumor heterogeneity, and clonal evolution. We believe that these efforts will improve patient prognoses. Herein, we discuss the current evidence of potential targets for systemic treatment, clinical considerations, and future perspectives.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.42 no.2
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• pp.111-118
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• 2016

Acne vulgaris is a chronic inflammatory condition characterized by comedo, papule, cyst, nodule and postinflammatory hyperpigmentation. Meanwhile, it is also induced by adverse event of drugs. Among them, acneiform folliculitis is a side effect of epidermal growth factor receptor (EGFR) inhibitor, which is an anticancer agent, and its incidence may occur in upward of 75 ~ 100% of cases. The main method of acne vulgaris treatment is oral antibiotics, retinoids, topical medication and so on. However, it is limitation that teratogenicity caused by retinoids and antibiotic resistance increased by using antibiotics. In this study, we aimed to evaluate the clinical efficacy and safety of topical recombinant human (rh) EGF in treating facial acne vulgaris. Twenty three Koreans (age: 10 ~ 29 years) with mild to moderate acne vulgar participated in the study and applied topical rhEGF cream (trouble control EGF) with 3 products (trouble control clarifying cleansing foam, trouble control all-clear filling toner, redroll calming moisture) on their face twice daily for four weeks. Several assessment methods were applied: Acne lesion counts score by investigator's global assessment, efficacy and satisfaction score by subjects. Skin sebum output level, hydration level and redness level were also measured at each visit. At the final visit, skin sebum level, transepidermal water loss, skin redness statistically decreased and acne lesions (comedone, papule) were statistically reduced. No severe side effects were observed during the study. In conclusion, topical rhEGF seems to be an effective and safe adjuvant treatment option for mild acne vulgaris.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.34 no.1
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• pp.59-70
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• 2008

Purpose: We evaluated the therapeutic effect of AEE788, a dual inhibitor of epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) receptor tyrosine kinases on human salivary adenoid cystic carcinoma (ACC) cells growing in nude mice. Experimental Design: We examined the effects of AEE788 on salivary ACC cell growth and apoptosis. To determine the in vivo effects of AEE788, nude mice with orthotopic parotid tumors were randomized to receive oral AEE788 (50 mg/kg) three times per week, injected paclitaxel ($200{\mu}g$) once per week, AEE788 plus paclitaxel, or placebo. Mechanisms of in vivo AEE788 activity were determined by immunohistochemical analysis. Results: Treatment of salivary ACC cells with AEE788 led to growth inhibition and induction of apoptosis. AEE788 inhibited tumor growth and prevented lung metastasis in nude mice. Furthermore, AEE788 potentiated growth inhibition and apoptosis of ACC tumor cells mediated by paclitaxel. Tumors of mice treated with AEE788 and AEE788 plus paclitaxel exhibited down-regulation of activated EGFR and its downstream mediators (Akt and MAPK), increased tumor and endothelial cell apoptosis, and decreased microvessel den-sity, which correlated with a decrease in the level of MMP-9, MMP-2 and bFGF expression and a decrease in the incidence of vascular metastasis. Conclusions: These data show that tumor-associated endothelial cells are important in the process of tumor-metastasis. And VEGFR can be a molecular target for therapy of metastatic lung lesion of salivary ACC.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.1
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• pp.495-498
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• 2013

Epidermal growth factor receptor (EGFR) is over-expressed in several human cancers. This would suggest that inhibition of EGFR is a reasonable approach for cancer treatment. In this study we investigated EGFR blocking and its effects on the mediated signaling such as MAPK and STATb in HT29 cells. For this aim we used FITC-labeled EGFR antisense oligonucleotides encapsulated with PAMAM nanoparticles to inhibit EGFR expression. Cellular uptake of antisense was investigated by fluorescence microscopy and flow cytometry analysis. The effect of EGFR antisense on the expression of EGFR in HT29 cells was examined by real time PCR and Western blots, which showed that antisense encapsulated with PAMAM decreased the level of EGFR mRNA and protein. In addition, real time PCR results confirmed that EGFR inhibition had an effective role in the reduction of EGFR dependent downstream genes. In conclusion, EGFR antisense encapsulated with PAMAM nanoparticles down regulated EGFR and EGFR-mediated genes.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.17 no.4
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• pp.331-336
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• 1995

To use cultured mucosa as a graft of full thickness, our laboratory has been involved in the development of techniques to grow epidermis together with connective tissue. Human oral mucosa was obtained at dental surgery. Under sterile conditions the tissues were cut into explants of 0.1 $cm^2$ which were placed in the center of 24 well tissue culture dishes and incubated in a growth medium. The growth medium used for epithelial was MEM(Minimum Essential Medium) supplemented with 10% fetal calf serum, 0.5% dimethyl sulfoxide, glutamine (0.292 g/l), epidermal growth factor (40 ug/ml), cholera toxin (30 ng/ml), hydrocortisone (2 ug/ml), insulin (40 ug/ml) and transferin (5 ug/ml). The medium for stratification of epithelial cells was MEM supplemented with 10% fetal calf serum, 0.5% dimethyl sulfoxide and glutamine (0.292 g/l). The medium used for fibroblasts was MEM supplemented with 10% fetal calf serum. With the three types of media used alternatively, a mucosa composed of epidermis and connective tissue was obtained after 3 weeks of culture.