• Tuberculosis and Respiratory Diseases
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• v.57 no.2
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• pp.160-168
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• 2004

Background : The role of second-line chemotherapy in the treatment of advanced non-small cell lung cancer (NSCLC) is known to be limited. Recently, ZD1839, the small molecule epidermal growth factor receptor-tyrosine kinase inhibitor, has been developed and has shown anti-tumor activity in patients with solid malignant tumors including lung cancer. We evaluated the response rate and toxicities of ZD1839 in patients with advanced NSCLC which has progressed after previous chemotherapy. Patients and Methods : We examined 83 patients with advanced NSCLC treated with ZD1839 for more than 1 month in Korea Cancer Center Hospital during the period from January 2002 to September 2003. All the patients were enrolled in the international expanded access program (EAP) with ZD1839 by AstraZeneca. The administered dose of ZD1839 was 250 mg once daily. Chest radiography and laboratory tests were followed-up. We evaluated the response rate, median survival, and toxicity after treatment. Results : Median age of the patients was 59 years (range 33-76). The most predominant cell type was adenocarcinoma and the most stage of the patients was IV. ECOG performance status was as follows; grade 0-1 in 10, grade 2 in 42, and grade 3 in 31 patients. Partial response was achieved in 12 patients (14.5%). Median overall survival was 9.2 (range 1.3-21.6+) months and median time to progression was 3.1 (range 1-21.2+) months. The most common adverse effect of ZD1839 was skin eruption which developed in 25 patients (25.8%). Significantly higher response rate and survival was found in patients with adenocarcinoma or good performance status. Conclusion : ZD1839 showed modest activity and tolerable toxicity in the treatment for patients with NSCLC which has progressed after previous chemotherapy.

• Genomics & Informatics
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• v.16 no.2
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• pp.36-41
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• 2018

Kawasaki disease (KD) is an acute febrile vasculitis predominately affecting infants and children. The dominant incidence age of KD is from 6 months to 5 years of age, and the incidence is unusual in those younger than 6 months and older than 5 years of age. We tried to identify genetic variants specifically associated with KD in patients younger than 6 months or older than 5 years of age. We performed an age-stratified genome-wide association study using the Illumina HumanOmni1-Quad BeadChip data (296 cases vs. 1,000 controls) and a replication study (1,360 cases vs. 3,553 controls) in the Korean population. Among 26 candidate single nucleotide polymorphisms (SNPs) tested in replication study, only a rare nonsynonymous SNP (rs4365796: c.1106C>T, p.Thr369Met) in the lymphoid enhancer binding factor 1 (LEF1) gene was very significantly associated with KD in patients younger than 6 months of age (odds ratio [OR], 3.07; $p_{combined}=1.10{\times}10^{-5}$), whereas no association of the same SNP was observed in any other age group of KD patients. The same SNP (rs4365796) in the LEF1 gene showed the same direction of risk effect in Japanese KD patients younger than 6 months of age, although the effect was not statistically significant (OR, 1.42; p = 0.397). This result indicates that the LEF1 gene may play an important role as a susceptibility gene specifically affecting KD patients younger than 6 months of age.

• Asia-Pacific Journal of Business Venturing and Entrepreneurship
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• v.15 no.2
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• pp.81-96
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• 2020

The purpose of this study is to investigate the impact of entrepreneurial mentoring as an effective support method to increase the awareness and entrepreneurial intention of university students. Therefore, the mediating effect of social support and entrepreneurial self-efficacy was demonstrated in the relationship between entrepreneurial mentoring and entrepreneurial intention. As a result of the analysis, the positive role of entrepreneurial mentoring was confirmed as an influencing factor to increase the intention of young prospective entrepreneurs to set up and increase their expectations for social support. Specifically, entrepreneurial mentoring had a significant positive effect on entrepreneurial intention, social support, and entrepreneurial self-efficacy. Social support had a significant positive effect on entrepreneurial self-efficacy and entrepreneurial intention, respectively, and partially mediated the relationship between entrepreneurial mentoring and entrepreneurial intention. Entrepreneurial self-efficacy had a positive effect on entrepreneurial intention, and entrepreneurial self-efficacy fully mediated between entrepreneurial mentoring and entrepreneurial intention. Through this study, it was proved that entrepreneurial mentoring is an important factor that positively influences entrepreneurial intention, social support, and entrepreneurial self-efficacy. In addition, by identifying the effect of social support on entrepreneurial self-efficacy, it was confirmed that the individual's self-confidence and efficacy increased when they recognized the belief or utilization of social support. Finally, by confirming that entrepreneurial mentoring has a positive effect on social support and that social support mediates between entrepreneurial mentoring and entrepreneurial intention, the entrepreneurial mentoring program raises the entrepreneurial intention to start a business and helps founders to social support. It has been confirmed that it can be used as a way to raise the awareness and effect of startup supporting policy in practice as well.

• Asia pacific journal of information systems
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• v.19 no.1
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• pp.33-62
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• 2009

Internet computing is a disruptive IT innovation. Semantic Web can be considered as an IT innovation because the Semantic Web technology possesses the potential to reduce information overload and enable semantic integration, using capabilities such as semantics and machine-processability. How should organizations adopt the Semantic Web? What factors affect the adoption and diffusion of Semantic Web innovation? Most studies on adoption and diffusion of innovation use empirical analysis as a quantitative research methodology in the post-implementation stage. There is criticism that the positivist requiring theoretical rigor can sacrifice relevance to practice. Rapid advances in technology require studies relevant to practice. In particular, it is realistically impossible to conduct quantitative approach for factors affecting adoption of the Semantic Web because the Semantic Web is in its infancy. However, in an early stage of introduction of the Semantic Web, it is necessary to give a model and some guidelines and for adoption and diffusion of the technology innovation to practitioners and researchers. Thus, the purpose of this study is to present a model of adoption and diffusion of the Semantic Web and to offer propositions as guidelines for successful adoption through a qualitative research method including multiple case studies and in-depth interviews. The researcher conducted interviews with 15 people based on face-to face and 2 interviews by telephone and e-mail to collect data to saturate the categories. Nine interviews including 2 telephone interviews were from nine user organizations adopting the technology innovation and the others were from three supply organizations. Semi-structured interviews were used to collect data. The interviews were recorded on digital voice recorder memory and subsequently transcribed verbatim. 196 pages of transcripts were obtained from about 12 hours interviews. Triangulation of evidence was achieved by examining each organization website and various documents, such as brochures and white papers. The researcher read the transcripts several times and underlined core words, phrases, or sentences. Then, data analysis used the procedure of open coding, in which the researcher forms initial categories of information about the phenomenon being studied by segmenting information. QSR NVivo version 8.0 was used to categorize sentences including similar concepts. 47 categories derived from interview data were grouped into 21 categories from which six factors were named. Five factors affecting adoption of the Semantic Web were identified. The first factor is demand pull including requirements for improving search and integration services of the existing systems and for creating new services. Second, environmental conduciveness, reference models, uncertainty, technology maturity, potential business value, government sponsorship programs, promising prospects for technology demand, complexity and trialability affect the adoption of the Semantic Web from the perspective of technology push. Third, absorptive capacity is an important role of the adoption. Fourth, suppler's competence includes communication with and training for users, and absorptive capacity of supply organization. Fifth, over-expectance which results in the gap between user's expectation level and perceived benefits has a negative impact on the adoption of the Semantic Web. Finally, the factor including critical mass of ontology, budget. visible effects is identified as a determinant affecting routinization and infusion. The researcher suggested a model of adoption and diffusion of the Semantic Web, representing relationships between six factors and adoption/diffusion as dependent variables. Six propositions are derived from the adoption/diffusion model to offer some guidelines to practitioners and a research model to further studies. Proposition 1 : Demand pull has an influence on the adoption of the Semantic Web. Proposition 1-1 : The stronger the degree of requirements for improving existing services, the more successfully the Semantic Web is adopted. Proposition 1-2 : The stronger the degree of requirements for new services, the more successfully the Semantic Web is adopted. Proposition 2 : Technology push has an influence on the adoption of the Semantic Web. Proposition 2-1 : From the perceptive of user organizations, the technology push forces such as environmental conduciveness, reference models, potential business value, and government sponsorship programs have a positive impact on the adoption of the Semantic Web while uncertainty and lower technology maturity have a negative impact on its adoption. Proposition 2-2 : From the perceptive of suppliers, the technology push forces such as environmental conduciveness, reference models, potential business value, government sponsorship programs, and promising prospects for technology demand have a positive impact on the adoption of the Semantic Web while uncertainty, lower technology maturity, complexity and lower trialability have a negative impact on its adoption. Proposition 3 : The absorptive capacities such as organizational formal support systems, officer's or manager's competency analyzing technology characteristics, their passion or willingness, and top management support are positively associated with successful adoption of the Semantic Web innovation from the perceptive of user organizations. Proposition 4 : Supplier's competence has a positive impact on the absorptive capacities of user organizations and technology push forces. Proposition 5 : The greater the gap of expectation between users and suppliers, the later the Semantic Web is adopted. Proposition 6 : The post-adoption activities such as budget allocation, reaching critical mass, and sharing ontology to offer sustainable services are positively associated with successful routinization and infusion of the Semantic Web innovation from the perceptive of user organizations.

• Journal of Embryo Transfer
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• v.22 no.1
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• pp.1-7
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• 2007

This study was conducted to examine the role of intact cumulus cells during in vitro fertilization (IVF) on sperm penetration, male pronuclear (MPN) formation and subsequent embryo development of oocytes matured and fertilized in vitro. Cumulus-oocyte complexes obtained from the slaughtered gilt ovaries were matured for 44 h in TCM199 containing 10% porcine follicular fluid, epidermal growth factor and hormones. After maturation culture, denuded oocytes or oocytes with intact cumulus cells were coincubated with frozen-thawed boar semen for 8h in a modified tris-buffered medium containing 5mM caffeine and 10mM calcium chloride. Putative zygotes were fixed and examined for sperm penetration and MPN formation (Experiments $1{\sim}3$), or cultured in North Carolina State University-23 medium fo. 156 h (Experiment 3). In Experiment 1, sperm penetration was examined after insemination of denuded oocytes and oocytes with intact cumulus cells at the concentration of $7.5{\times}10^5$ sperm/ml. Optimal sperm concentration for IVF of cumulus-intact oocytes was determined in Experiment 2 by inseminating intact oocytes with $2{\sim}5{\times}10^6$ sperm/ml. In Experiment 3, denuded or intact oocytes were inseminated at the concentrations of $7.5{\times}10^5$ and $4.0{\times}10^6$ sperm/ml, respectively, and in vitro embryo development was compared. Sperm penetration was significantly (p<0.01) decreased in cumulus-intact oocytes compared to denuded oocytes (35.2% vs. 77.4%). Based on the rates of sperm penetration and normal fertilization, the concentration of $4.0{\times}10^6$ sperm/ml was optimal for the IVF of intact oocytes compared to other sperm concentrations. The presence of intact cumulus cells during IVF significantly (p<0.05) improved embryo cleavage (48.8% vs. 58.9%), blastocyst (BL) formation (11.0% vs. 22.8%) and embryo cell number $(22{\pm}2\;vs.\;29{\pm}2\;cells)$ compared to denuded oocytes. In conclusion, these results suggest that intact cumulus cells during IVF inhibit sperm penetration but improve embryo cleavage, BL formation and embryo cell number of porcine embryos produced in vitro.

• Childhood Kidney Diseases
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• v.6 no.2
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• pp.142-154
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• 2002

Purpose : One of the most important adverse effects of long-term cyclosporine therapy is nephrotoxicity, the morphologic changes of which include interstitial fibrosis and arteriolar hyalinization. Recently, several authors have shown that osteopontin plays an important role in the development of interstitial fibrosis by acting as a macrophage chemoattractant and stimulating the production of $TGF-{\beta}$ in experimental cyclosporine nephrotoxicity. However, the relationship between osteopontin and $TGF-{\beta}$ in humans has not been clearly documented so far. We studied the expression of osteopontin and $TGF-{\beta}$ in children with minimal change nephrotic syndrome treated with cyclosporine to demonstrate whether there is a relationship between cyclosporine toxicity and osteopontin expression as previously shown in animal models. Materials and methods : Nineteen children (15 males and 4 females) were the subject of this study. Renal biopsies had been performed before and after the cyclosporine therapy (mean duration: 15.9 months). In 5 patients, additional biopsies were performed after completing the cyclosporine treatment (mean; 26 months). The expressions of osteopontin and $TGF-{\beta}$ were evaluated by immunohistochemistry in the glomeruli and tubulointerstitium. Results : Osteopontin expression was significantly increased in the glomerular mesangium and tubules after cyclosporine treatment. But there was no statistically significant increase of $TGF-{\beta}$ in the interstitium. There was no significant increase in tubular osteopontin and interstitial $TGF-{\beta}$ expression in those cases developing interstitial fibrosis after cyclosporine treatment compared with cases those not developing interstitial fibrosis. No significant changes in osteopontin or $TGF-{\beta}$ expression were observed in subsequent 5 biopsy samples after discontinuation of cyclosporine compared with the first follow up biopsies. Conclusion : These results suggest that osteopontin is a nonspecific marker of renal injury rather than a mediator of interstitial fibrosis in cyclosporine nephrotoxicity of human.

• Radiation Oncology Journal
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• v.20 no.2
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• pp.130-138
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• 2002

Purpose : This study analyzed the prognostic factors affecting the survival rate and evaluated the role of radiation therapy in muscle-invading bladder cancer. Materials and Methods : Twenty eight patients with bladder cancer who completed planned definitive radiotherapy in the Departments of Therapeutic Radiology and Urology, Chonnam National University Hospital between Jan. 1986 to Dec. 1998 were retrospectively analyzed. The reviews were peformed based on the patients' medical records. There were 21 males and 7 females in this study. The median of age was 72 years old ranging from 49 to 84 years. All patients were confirmed as having transitional cell carcinoma with histological grade 1 in one patient, grade 2 in 15, grade 3 in 9, and uninformed in 3. Radiation therapy was peformed using a linear accelerator with 6 or 10 MV X-rays. Radiation was delivered daily with a 1.8 or 2.0 Gy fraction size by 4 ports (anterior-posterior, both lateral, alternatively) or 3 ports (Anterior and both lateral). The median radiation dose delivered to the isocenter of the target volume was 61.24 Gy ranging from 59 to 66.6 Gy. The survival rate was calculated by the Kaplan-Meier method. Multivariate analysis was peformed on the prognostic factors affecting the survival rate. Results : The survival rate was $76\%,\;46\%,\;33\%,\;33\%$ at 1, 2, 3, 5 years, respectively, with 19 months of median survival. The potential factors of age (less than 70 years vs above 70), sex, diabetes mellitus, hypertension, hydronephrosis, 1-stage (T3a vs T3b), TUR, chemotherapy, total duration of radiotherapy, radiation dose (less than 60 Gy vs above 60 Gy), and the treatment response were investigated with uniand multivariate analysis. Un univariate analysis, the T-stage (p=0.078) and radiation dose (p=0.051) were marginally significant, and the treatment response (p=0.011) was a statistically significant factor on the survival rate. Multivariate analysis showed there were no significant prognostic factors affecting the survival rate. Conclusion : The treatment response and radiation dose are suggested as th은 statistically significant factors affecting the survival rate of muscle invasive bladder cancer. A Further prospective randomized study is needed to confirm these prognostic factors.

• Radiation Oncology Journal
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• v.15 no.3
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• pp.225-231
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• 1997

Purpose : Radiation therapy in combination with surgery has an important role in the therapy of the head and neck cancer We conducted a prospective study for patients with head and neck cancer treated with surgery and radiation to evaluate the effect of therapies on the thyroid gland, and to identify the factors that might influence the development of hypothyroidism. Materials and Methods : From September 1986 through December 1994, 71 patients with head and cancer treated with surgery and radiation were included in this prospective study. Patients' age ranged from 32 to 73 years with a median age of 58 years. There were 12 women and 59 men. The primary tumor sites were larynx in 34 patients, hypopharynx in 13 patients, oral cavity in 12 patients, unknown primary of the neck in 6 patients, salivary gland in 3 patients, maxillary sinus in 2 patients, and oropharynx in 1 patient. Total laryngectomy with neck dissection was carried out in 45 patients and neck dissection alone in 26 patients. All patients were serially monitored for thyroid function (T3, T4, free T4, TSH, antithyroglobulin antibody and antimicrosomal antibody) before and after radiation therapy. Radiation dose to the thyroid gland ranged from 40.6Gy to 60Gy with a median dose of 50Gy The follow-up duration was 3 to 80 months. Results :The overall incidence of hypothyroidism was 56.3\%$);7 out of 71 patients $(9.9\%)$ developed clinical hypothyroidism and 33 patients $(46.4\%)$ developed subclinical hypothyroidism. No thyroid nodules, thyroid cancers, or hyperthyroidism was detected. Hypothyroidism developed earlier in patients who underwent total laryngectomy with neck dissection than in patients with neck dissection alone (P<0.05). The risk factor that significantly influenced the incidence of hypothyroidism was a combination of surgery (total laryngectomy with neck dissection) and radiation therapy (P=0.0000), Four of 26 patients $(15.4\%)$ with neck dissection alone developed hypothyroidism while 36 of 45 patients $(80\%)$ with laryngectomy and neck dissection developed hypothyroidism. Conclusion : The hypothyroidism following surgery and radiation therapy was a relatively common complication. The factor that significantly influenced theincidence of hypothyroidism was combination of surgery and radiation therapy. Evaluation of thyroid function before and after radiation therapy with periodic thyroid function tests is recommended for an early detection of hypothyroidism and thyroid hormone replacement therapy is recommended whenever hypothyroidism develops.

• Asian-Australasian Journal of Animal Sciences
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• v.18 no.5
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• pp.747-754
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• 2005

Nutritional regulation of gene expression associated with growth and feeding behavior in avian species can become an important technique to improve poultry production according to the supply of nutrients in the diet. Insulin-like growth factor-I (IGF-I) found in chickens has been characterized to be a 70 amino acid polypeptide and plays an important role in growth and metabolism. Although it is been well known that IGF-I is highly associated with embryonic development and post-hatching growth, changes in the distribution of IGF-I gene expression throughout early- to late-embryogenesis have not been studied so far. We revealed that the developmental pattern of IGF-I gene expression during embryogenesis differed among various tissues. No bands of IGF-I mRNA were detected in embryonic liver at 7 days of incubation, and thereafter the amount of hepatic IGF-I mRNA was increased from 14 to 20 days of incubation. In eyes, a peak in IGF-I mRNA levels occurred at mid-embryogenesis, but by contrast, IGF-I mRNA was barely detectable in the heart throughout all incubation periods. In the muscle, no significant difference in IGF-I gene expression was observed during different stages of embryogenesis. After hatching, hepatic IGF-I gene expression as well as plasma IGF-I concentration increases rapidly with age, reaches a peak before sexual maturity, and then declines. The IGF-I gene expression is very sensitive to changes in nutritional conditions. Food-restriction and fasting decreased hepatic IGF-I gene expression and refeeding restored IGF-I gene expression to the level of fed chickens. Dietary protein is also a very strong factor in changing hepatic IGF-I gene expression. Refeeding with dietary protein alone successfully restored hepatic IGF-I gene expression of fasted chickens to the level of fed controls. In most circumstances, IGF-I makes a complex with specific high-affinity IGF-binding proteins (IGFBPs). So far, four different IGFBPs have been identified in avian species and the major IGFBP in chicken plasma has been reported to be IGFBP-2. We studied the relationship between nutritional status and IGFBP-2 gene expression in various tissues of young chickens. In the liver of fed chickens, almost no IGFBP-2 mRNA was detected. However, fasting markedly increased hepatic IGFBP-2 gene expression, and the level was reduced after refeeding. In the gizzard of well-fed young chickens, IGFBP-2 gene expression was detected and fasting significantly elevated gizzard IGFBP-2 mRNA levels to about double that of fed controls. After refeeding, gizzard IGFBP-2 gene expression decreased similar to hepatic IGFBP-2 gene expression. In the brain, IGFBP-2 mRNA was observed in fed chickens and had significantly decreased by fasting. In the kidney, IGFBP-2 gene expression was observed but not influenced by fasting and refeeding. Recently, we have demonstrated in vivo that gizzard and hepatic IGFBP-2 gene expression in fasted chickens was rapidly reduced by intravenous administration of insulin, as indicated that in young chickens the reduction in gizzard and hepatic IGFBP-2 gene expression in vivo stimulated by malnutrition may be, in part, regulated by means of the increase in plasma insulin concentration via an insulin-response element. The influence of dietary protein source (isolated soybean protein vs. casein) and the supplementation of essential amino acids on gizzard IGFBP-2 gene expression was examined. In both soybean protein and casein diet groups, the deficiency of essential amino acids stimulated chickens to increase gizzard IGFBP-2 gene expression. Although amino acid supplementation of a soybean protein diet significantly decreased gizzard IGFBP-2 mRNA levels, a similar reduction was not observed in chickens fed a casein diet supplemented with amino acids. This overview of nutritional regulation of IGF-I and IGFBP-2 gene expression in young chickens would serve for the establishment of the supply of nutrients to diets to improve poultry production.

• Clinical and Experimental Pediatrics
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• v.53 no.4
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• pp.525-531
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• 2010

Purpose : Expression levels of tumor necrosis factor (TNF)-${\alpha}$ expression on the mucosa of the small intestine is increased in patients with villous atrophy in food protein-induced enterocolitis syndrome (FPIES). TNF-${\alpha}$ has been reported to induce apoptotic cell death in the epithelial cells. We studied the TNF family and TNF-receptor family apoptosis on the duodenal mucosa to investigate their roles in the pathogenesis of FPIES. Methods : Fifteen infants diagnosed as having FPIES using standard oral challenge test and 5 controls were included. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining was performed to identify the apoptotic cell death bodies. Immunohistochemical staining of TNF-${\alpha}$, Fas ligand (FasL) for TNF family and TNF-related apoptosis-including ligand (TRAIL) receptor 1 (DR4), TRAIL receptor 2 (DR5), and Fas for TNF-receptor family were performed to determine the apoptotic mechanisms. Results : $TUNEL^+$ was significantly more highly expressed in the duodenal mucosa of FPIES patients than in controls ($P$-0.043). TNF-${\alpha}$ ($P$=0.0001) and DR4 ($P$=0.003) were significantly more highly expressed in FPIES patients than in controls. Expression levels of FasL, Fas, and DR5 were low in both groups and were not significantly different between the 2 groups. Conclusion : These results suggest that FPIES pathogenesis is induced by apoptosis, and that TNF-${\alpha}$ expression and DR4 pathway may have an important role in apoptosis.