• Clinical and Experimental Pediatrics
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• 제56권4호
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• pp.151-158
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• 2013

Purpose: We investigated the mRNA levels of peroxisome proliferator-activated receptor (PPAR)-${\alpha}$, PPAR-${\gamma}$, adipokines, and cytokines in the lung tissue of lean and obese mice with and without ovalbumin (OVA) challenge, and the effect of rosiglitazone, a PPAR-${\gamma}$ agonist. Methods: We developed 6 mice models: OVA-challenged lean mice with and without rosiglitazone; obese mice with and without rosiglitazone; and OVA-challenged obese mice with and without rosiglitazone. We performed real-time polymerase chain reaction for leptin, leptin receptor, adiponectin, vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF)-${\alpha}$, transforming growth factor (TGF)-${\beta}$, PPAR-${\alpha}$ and PPAR-${\gamma}$ from the lung tissue and determined the cell counts and cytokine levels in the bronchoalveolar lavage fluid. Results: Mice with OVA challenge showed airway hyperresponsiveness. The lung mRNA levels of PPAR${\alpha}$ and PPAR-${\gamma}$ increased significantly in obese mice with OVA challenge compared to that in other types of mice and decreased after rosiglitazone administeration. Leptin and leptin receptor expression increased in obese mice with and without OVA challenge and decreased following rosiglitazone treatment. Adiponectin mRNA level increased in lean mice with OVA challenge. Lung VEGF, TNF-${\alpha}$, and TGF-${\beta}$ mRNA levels increased in obese mice with and without OVA challenge compared to that in the control mice. However, rosiglitazone reduced only TGF-${\beta}$ expression in obese mice, and even augmented VEGF expression in all types of mice. Rosiglitazone treatment did not reduce airway responsiveness, but increased neutrophils and macrophages in the bronchoalveolar lavage fluid. Conclusion: PPAR-${\alpha}$ and PPAR-${\gamma}$ expressions were upregulated in the lung tissue of OVA-challenged obese mice however, rosiglitazone treatment did not downregulate airway inflammation in these mice.

• 수면정신생리
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• 제22권1호
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• pp.20-24
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• 2015

목 적 : 제 1형 당뇨병을 진단 받은 소아 청소년 환자들을 대상으로 RLS를 평가하고 RLS를 동반하는 환자군과 RLS를 동반하지 않은 환자군 간의 임상적 변인과 수면의 특성을 비교하고자 하였다. 방 법 : 소아 청소년과에서 제 1형 당뇨병으로 진단 받은 7세 이상 18세 이하의 소아 청소년 55명을 대상으로 면담, 설문조사, 임상학적 검사를 시행하였다. RLS 진단은 IRLSSG 진단기준을 따랐으며 설문은 Epworth sleepiness scale (ESS), International restless legs syndrome rating scale (IRLSRS)를 이용하였다. 결 과 : 55명의 대상자 중 RLS 빈도는 13명으로 23.6%였다. RLS 관련 변인으로 BMI, Hb, Iron, ferritin, TIBC, creatinine, GFR에서 두 군간에 유의한 차이는 없었다. RLS 환자 13명 중 RLS 가족력을 가진 환자는 7명으로, RLS가 없는 환자의 경우와 현저한 차이를 보였다. 수면의 특성을 조사한 결과 RLS를 동반한 환자군이 RLS를 동반하지 않은 군에 비해 ESS, IRLSRS 결과가 유의하게 높았다. 결 론 : 제 1형 당뇨병을 진단 받은 소아 청소년은 RLS가 흔히 동반되었다. 임상적으로 당뇨 소아 청소년의 RLS 동반여부와 수면의 질을 평가하여 치료하는 것이 필요하겠으며 향후 보다 많은 환자를 대상으로 보다 객관적인 방법을 이용한 연구가 진행되어야 할 것이다.

• Biomolecules & Therapeutics
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• 제24권2호
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• pp.132-139
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• 2016

The endothelial-mesenchymal transition (EndMT) is known to be involved in the transformation of vascular endothelial cells to mesenchymal cells. EndMT has been confirmed that occur in various pathologic conditions. Transforming growth factor ${\beta}1$ (TGF-${\beta}1$) is a potent stimulator of the vascular endothelial to mesenchymal transition (EMT). Aspirin-triggered resolvin D1 (AT-RvD1) has been known to be involved in the resolution of inflammation, but whether it has effects on TGF-${\beta}1$-induced EndMT is not yet clear. Therefore, we investigated the effects of AT-RvD1 on the EndMT of human umbilical vein vascular endothelial cells line (HUVECs). Treatment with TGF-${\beta}1$ reduced the expression of Nrf2 and enhanced the level of F-actin, which is associated with paracellular permeability. The expression of endothelial marker VE-cadherin in HUVEC cells was reduced, and the expression of mesenchymal marker vimentin was enhanced. AT-RvD1 restored the expression of Nrf2 and vimentin and enhanced the expression of VE-cadherin. AT-RvD1 did also affect the migration of HUVEC cells. Inhibitory ${\kappa}B$ kinase 16 (IKK 16), which is known to inhibit the NF-${\kappa}B$ pathway, had an ability to increase the expression of Nrf2 and was associated with the inhibition effect of AT-RvD1 on TGF-${\beta}1$-induced EndMT, but it had no effect on TGF-${\beta}1$-induced EndMT alone. Smad7, which is a key regulator of TGF-${\beta}$/Smads signaling by negative feedback loops, was significantly increased with the treatment of AT-RvD1. These results suggest the possibility that AT-RvD1 suppresses the TGF-${\beta}1$-induced EndMT through increasing the expression of Smad7 and is closely related to oxidative stress.

• 생명과학회지
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• 제20권2호
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• pp.161-168
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• 2010

White-skinned sweet potato (WSP, Ipomoea batatas L.)는 일본, 인도네시아 등에서 당뇨병과 그 치료에 민간에서 사용되고 있다. 본 실험에서는 WSP의 메탄올 추출물을 체중 1 kg 당 Dose 100, 200 mg을 투여하여 streptozotocin으로 유발된 당뇨쥐에서 손상된 신장 보호효과를 평가하였고 그 효능을 인슐린 분비촉진제인 glimepiride (45 mg/kg 체중)와 비교해 보았다. WSP 메탄올 추출물과 glimepiride를 2주 투여 한 후 혈당, 혈중 요소성 질소(BUN), 크레아티닌, 젖산 탈수소효소(LDH), 지질 과산화물(LPO) 함량, 그리고 항산화효소들인 superoxide dismutase (SOD), 카탈라아제(CAT), 글루타치온 과산화물 분해효소(GPx), 글루타치온 S-전이효소(GST) 등의 활성도를 측정하였다. BUN, 크레아티닌, LDH, 혈당, LPO 함량 등은 대조군에 비하여 그 값이 증가하였고, SOD, CAT, GPx, GST 값은 감소하였다. WSP 메탄올 추출물(200 mg/kg)을 투여한 후 측정한 값은 혈당, LPO, 신장병 표지인자인 BUN, 크레아티닌, LDH, 그리고 지질 과산화물 함량에서 의미있는 개선효과를 볼 수 있었고 항산화효소, 항산화물질의 증가도 나타났다. 따라서 WSP 메탄올 추출물은 당뇨쥐의 혈당을 낮추며 산화적 스트레스를 약화시키고 당뇨로 유발된 신장 손상을 보호해 주는 효과가 있다는 결과를 얻었다. 또한 민간에서 사용하고 있는 WSP가 실제로 당뇨 치료에 효과가 있음을 과학적 증거로 제공해 주었다고 판단된다.

• Clinical and Experimental Reproductive Medicine
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• 제36권1호
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• pp.71-80
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• 2009

목 적: 다낭성 난소 증후군은 생식기 여성에서 나타나는 가장 흔한 내분비 질환 중 하나이며 다양한 임상 양상을 보이고 있다. 본 연구에서는 한국인 다낭성 난소 증후군 환자 특유의 임상 양상 및 혈액학적 소견을 밝히고자 하였으며 그 결과를 터키와 미국의 다낭성 난소 증후군 환자와 비교 분석하였다. 연구방법: 2000년 1월부터 2008년 4월까지 경북대학교 병원 불임치료실을 찾은 88명의 다낭성 난소 증후군 환자를 대상으로 하여 후향적으로 임상 양상 및 혈액학적 소견을 연구하였다. 결 과: 한국인 다낭성 난소 증후군 환자군 내에서는 통계학적으로 유의한 연령에 따른 임상 양상의 차이가 없었으나 터키와 미국의 다낭성 난소 증후군 환자와 비교했을 때 고안드로겐혈증의 빈도는 유의하게 낮았다. 결 론: 다낭성 난소 증후군 환자 내에서도 인종간의 임상 양상 및 혈액학 소견의 차이가 있다고 생각되며 유전 및 생활 습관의 차이 등이 그 원인을 설명할 수 있을 것이다. 그러나 연구 대상인 환자의 수가 적고 연령군의 분포가 좁아 향후 좀 더 큰 규모의 연구가 필요하다.

• Clinical and Experimental Reproductive Medicine
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• 제47권3호
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• pp.194-206
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• 2020

Objective: The aim of this study was to investigate microRNAs (miRNAs) related to follicle-stimulating hormone (FSH) responsiveness using miRNA microarrays and to identify their target genes to determine the molecular regulatory pathways involved in FSH signaling in KGN cells. Methods: To change the cellular responsiveness to FSH, KGN cells were treated with FSH receptor (FSHR)-specific small interfering RNA (siRNA) followed by FSH. miRNA expression profiles were determined through miRNA microarray analysis. Potential target genes of selected miRNAs were predicted using bioinformatics tools, and their regulatory function was confirmed in KGN cells. Results: We found that six miRNAs (miR-1261, miR-130a-3p, miR-329-3p, miR-185-5p, miR-144-5p and miR-4463) were differentially expressed after FSHR siRNA treatment in KGN cells. Through a bioinformatics analysis, we showed that these miRNAs were predicted to regulate a large number of genes, which we narrowed down to cytochrome P450 family 19 subfamily A member 1 (CYP19A1) and estrogen receptor alpha (ESR1) as the main targets for miR-4463. Functional analysis revealed that miR-4463 is a regulatory factor for aromatase expression and function in KGN cells. Conclusion: In this study, we identified differentially expressed miRNAs related to FSH responsiveness. In particular, upregulation of miR-4463 expression by FSHR deficiency in human granulosa cells impaired 17β-estradiol synthesis by targeting CYP19A1 and ESR1. Therefore, our data might provide novel candidates for molecular biomarkers for use in research into poor responders.

• 의학교육논단
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• 제17권2호
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• pp.78-87
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• 2015

Mongolia is suffering from the inadequate capacity of medical doctors due to a poor education and training system. The purpose of this article is to evaluate the effect of a clinical training program for capacity building of medical doctors in Mongolia, and to suggest an effective model for continuing professional development in developing countries. Based on the results of a needs assessment, Korean and Mongolian medical experts developed a clinical training program and trained the trainers on 32 topics regarding major clinical problems in 6 specialties, including cardiology, endocrinology, pediatrics, obstetrics and gynecology, neurology, and emergency medicine. Surveillance survey and pre/post-test were used on every topic to evaluate the satisfaction and achievement, respectively, of the trainees. Six months after the clinical training program, we interviewed a sample of medical professionals to evaluate the change and impact. A total of 612 (person-year) medical doctors participated in the training, and the average score for satisfaction was 7.69 out of 8. The average score of the pre-test was 46.9 out of 100, while the post-test was 82.4. After the training, the medical doctors were applying their new knowledge and skills to their practice, and using the materials as guidelines, which improved their practice and increased patient satisfaction. They also started their own training program and adopted new equipment at their hospitals. The satisfaction and achievement of the trainees were very high, and there was significant change in the medical practice, education system, and infrastructure after the training program. This training program can be an effective model for capacity building of medical doctors in developing countries.

• Asian Pacific Journal of Cancer Prevention
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• 제16권4호
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• pp.1431-1434
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• 2015

Background: Breast cancer is one of the most common cancers among women worldwide and the HER2 receptor plays an important role in its development and progression. This systematic review aimed to summarize the role of HER2 in brain metastasis in patients with breast cancer. Materials and Methods: We conducted a literature search by advanced search in title field using the Scopus, Pubmed, and Google scholar databases until the end of June 2014. With metastasis, metastatic, HER2, brain, and breast cancer, as terms of search we selected 31 articles, which were reviewed by two independent and blinded expert reviewers. The studies were first selected according to their titles and abstracts. Quality of the studies were then assessed using the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) protocol for observational studies and CONSORT(Consolidation of Standards for Reporting Trials) protocol for clinical trials. For statistical analyses, we used STATA, version 11.0 software. Forest and funnel diagrams were drawn and for heterogeneity, index was also considered. Also we used meta regression analysis. Results: Finally, we reviewed 10 studies. The prevalence of brain metastasis in HER2-positive breast cancer patients was 24.9%. There was publication bias in the reviewed studies. Meta regression analysis showed that follow up time had no significant effect (p=0.396) on the prevalence of brain metastasis. Conclusions: The results showed a high prevalence of brain metastasis in HER2 positive breast cancer patients.

• Asian Pacific Journal of Cancer Prevention
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• 제17권7호
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• pp.3431-3436
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• 2016

Background: Carcinogenesis is a multifaceted intricate cellular mechanism of transformation of the normal functions of a cell into neoplastic alterations. Metastasis may result in failure of conventional treatment and death Hence, research on metastatic suppressors in cancer is a high priority. The metastatic suppressor gene CD82, also known as KAI1, is a member of the transmembrane 4 superfamily which was first identified in carcinoma of prostate. Little work has been done on this gene in breast cancer. Herein, we aimed to determine the gene and protein level expression of CD82/KAI1 in breast cancer and its role as a prognosticator. Materials and Methods: In this study, 83 histologically proven cases of breast cancer and a similar number of controls were included. Patient age ranged from 18-70 years. Quantitative Real Time Polymerase Chain Reaction (q-RT PCR) and immunohistochemistry (IHC) were used to investigate KAI1 expression at gene and protein levels, respectively. Statistical analysis was done to correlate expression of KAI1 and clinicopathological parameters. Results: It was revealed that: (i) KAI1 was remarkably diminished in metastatic vs non metastatic breast cancer both at the gene and the protein levels (P < .05); (ii) KAI1 expression levels were strongly correlated with TNM staging, histological grade and advanced stage (p<0.001) and no association was found with any other studied parameter; (iii) Lastly, a significant correlation was observed between expression of KAI1 and overall median survival of BC patients (P = 0.04). Conclusions: Our results suggest that lack of expression of the KAI1 might indicate a more aggressive form of breast cancer. Loss of KAI1 may be considered a significant prognostic marker in predicting metastatic manifestation. When evaluated along with the clinical and pathological factors, KAI1 expression may be beneficial to tailor aggressive therapeutic strategies for such patients.

• Clinical and Experimental Pediatrics
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• 제54권6호
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• pp.253-259
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• 2011

Purpose: Long-term survivors of childhood cancer appear to have an increased risk for the metabolic syndrome, subsequent type 2 diabetes and cardiovascular disease in adulthood compared to healthy children. The purpose of this study was to investigate the frequency of the metabolic syndrome and associated factors in childhood cancer survivors at a single center in Korea. Methods: We performed a retrospective review of medical records of 98 childhood cancer survivors who were diagnosed and completed anticancer treatment at Samsung Medical Center, Seoul, Korea between Jan. 1996 and Dec. 2007. Parameters of metabolic syndrome were evaluated between Jan. 2008 and Dec. 2009. Clinical and biochemical findings including body fat percentage were analyzed. Results: A total of 19 (19.4%) patients had the metabolic syndrome. The median body fat percentage was 31.5%. The body mass index and waist circumference were positively correlated with the cranial irradiation dose (r=0.38, P<0.001 and r=0.44, P<0.00, respectively). Sixty-one (62.2%) patients had at least one abnormal lipid value. The triglyceride showed significant positive correlation with the body fat percentage (r=0.26, P=0.03). The high density lipoprotein cholesterol showed significant negative correlation with the percent body fat (r=- 0.26, P=0.03). Conclusion: Childhood cancer survivors should have thorough metabolic evaluation including measurement of body fat percentage even if they are not obese. A better understanding of the determinants of the metabolic syndrome during adolescence might provide preventive interventions for improving health outcomes in adulthood.