• Molecules and Cells
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• 제40권1호
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• pp.45-53
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• 2017

Aberrant hypermethylation of Wnt antagonists has been observed in gastric cancer. A number of studies have focused on the hypermethylation of a single Wnt antagonist and its role in regulating the activation of signaling. However, how the Wnt antagonists interacted to regulate the signaling pathway has not been reported. In the present study, we systematically investigated the methylation of some Wnt antagonist genes (SFRP2, SFRP4, SFRP5, DKK1, DKK2, and APC) and their regulatory role in carcinogenesis. We found that aberrant promoter methylation of SFRP2, SFRP4, DKK1, and DKK2 was significantly increased in gastric cancer. Moreover, concurrent hypermethylation of SFRP2 and DKK2 was observed in gastric cancer and this was significantly associated with increased expression of ${\beta}-catenin$, indicating that the joint inactivation of these two genes promoted the activation of the Wnt signaling pathway. Further analysis using a multivariate Cox proportional hazards model showed that DKK2 methylation was an independent prognostic factor for poor overall survival, and the predictive value was markedly enhanced when the combined methylation status of SFRP2 and DKK2 was considered. In addition, the methylation level of SFRP4 and DKK2 was correlated with the patient's age and tumor differentiation, respectively. In conclusion, epigenetic silencing of Wnt antagonists was associated with gastric carcinogenesis, and concurrent hypermethylation of SFRP2 and DKK2 could be a potential marker for a prognosis of poor overall survival.

• Clinics in Shoulder and Elbow
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• 제26권1호
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• pp.32-40
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• 2023

Background: The purpose of this study was to identify predictors of the time from initial presentation to total shoulder arthroplasty (TSA) in patients with primary glenohumeral osteoarthritis (OA) and rotator cuff (RTC) arthropathy who were conservatively managed with corticosteroid injections. Methods: We conducted a retrospective cohort study of patients who underwent TSA from 2010 to 2021. Kaplan-Meier survival analysis was used to estimate median time to TSA for primary OA and RTC arthropathy patients. The Cox proportional hazards model was used to identify significant predictors of time to TSA and to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). Statistical significance was set at P<0.05. Results: The cohort included 160 patients with primary OA and 92 with RTC arthropathy. In the primary OA group, median time to TSA was 15 months. Significant predictors of shorter time to TSA were older age at presentation (HR, 1.02; 95% CI, 1.00-1.04; P=0.03) and presence of moderate or severe acromioclavicular joint arthritis (HR, 1.45; 95% CI, 1.05-2.01; P=0.03). In the RTC arthropathy group, median time to TSA was 14 months, and increased number of corticosteroid injections was associated with longer time to TSA (HR, 0.87; 95% CI, 0.80-0.95; P=0.003). Conclusions: There are distinct prognostic factors for progression to TSA between primary OA patients and RTC arthropathy patients managed with corticosteroid injections. Multiple corticosteroid injections are associated with delayed time to TSA in RTC arthropathy patients.

• 한국산학기술학회논문지
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• 제20권10호
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• pp.425-432
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• 2019

본 연구는 한국언론진흥재단 BIGKinds를 통해 수집한 구제역 등의 축산 질병 관련 보도가 소비자의 육류소비에 미치는 영향요인들을 알아보기 위하여 생존 분석을 이용하여 분석하였다. 소비자 구매자료는 농촌진흥청의 농식품 소비자 패널조사 자료를 이용하였으며, 생존시간에 대한 분석결과 국내산 소고기와 돼지고기, 수입산 소고기와 돼지고기 모두에서 FMD(구제역) 보도가 유의한 영향을 미치며, FMD(구제역) 관련 보도로 인해 첫 구매율이 감소한 것으로 나타났다. 시간 의존 Cox 비례 해저드 모형을 이용하여 세부적으로 분석한 결과 모든 모형은 5% 유의수준에서 유의한 것으로 분석되었다. 각 모형에서 공통적으로 유의한 것으로 분석된 것은 FMD 관련 보도 건수로 나타났다. 2010년 국내산과 수입산 돼지고기의 Haz. Ratio는 5% 유의수준에서 0.999로 나타나 FMD 관련 보도가 1건 증가할 때마다 첫 구매율은 0.999배 감소한 것으로 분석되었다. 반면 2015년 돼지고기의 Haz. Ratio는 2010년과는 다르게 1.001로 나타나 오히려 첫 구매율이 증가한 것으로 분석되었다. 소고기의 경우에도 돼지고기와 비슷한 결과가 나타났다. 본 연구는 소비자의 육류소비에 질병 관련 보도가 첫 구매에 어떠한 영향을 미치는지에 대해 원산지별, 육류별로 추정하여 보다 합리적인 생산 및 소비 활동에 필요한 정보를 제공하는 데 의의를 가지고 있다. 또한, 축산 질병 관련 보도가 지속되는 시간을 추정하여 제시함으로써 소비 판촉 등의 홍보에도 반영할 수 있을 것으로 여겨진다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권5호
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• pp.1839-1843
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• 2015

Background: MicroRNAs are a class of noncoding RNAs which regulate multiple cellular processes during tumor development. The purpose of this report is to investigate the clinicopathological and prognostic significance of miR-218 in human gliomas. Materials and Methods: Quantitative RT-PCR (qRT-PCR) was conducted to detect the expression of miR-218 in primary normal human astrocytes, three glioma cell lines and 98 paired glioma and adjacent normal brain tissues.Associations of miR-218 with clinicopathological variables of glioma patients were statistically analyzed. Finally, a survival analysis was performed using the Kaplan-Meier method and Cox's proportional hazards model. Results: The expression level of miR-218 in primary normal human astrocytes was significantly higher than that in glioma cell lines (p<0.01). Also, the expression level of miR-218 in glioma tissues was significantly downregulated in comparison with that in the adjacent normal brain tissues (p<0.001). Statistical analyses demonstrated that low miR-218 expression was closely associated with advanced WHO grade (p=0.002) and low Karnofsky performance score (p=0.010) of glioma patients. Kaplan-Meier analysis with the log-rank test showed that patients with low-miR-218 expression had poorer disease-free survival and overall survival (p=0.0045 and 0.0124, respectively). Multivariate analysis revealed that miR-218 expression was independently associated with the disease-free survival (p=0.009) and overall survival (p=0.004) of glioma patients. Conclusions: Our results indicate that miR-218 is downregulated in gliomas and that its status might be a potential valuable biomarker for glioma patients.

• Asian Pacific Journal of Cancer Prevention
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• 제13권5호
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• pp.2219-2224
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• 2012

Background: Circulating lymphocyte subsets reflect the immunological status and might therefore be a prognostic indicator in cancer patients. Our aim was to evaluate the clinical significance of circulating lymphocyte subset in gastric cancer (GC) cases. Methods: A retrospective study on a prevalent cohort of 846 GC patients hospitalized at Hospital from Aug 2006 to Jul 2010 was conducted. We calculated the patient's disease free survival (DFS) after first hospital admission, and hazard ratios (HR) from the Cox proportional hazards model. Results: Our findings indicated a significantly decreased percentage of CD3+, and CD8+ cells, a significantly increased proportion of $CD4^+$, $CD19^+$, $CD44^+$, $CD25^+$, NK cells, and an increased $CD4^+/CD8^+$ ratio in GC patients as compared with healthy controls (all P < 0.05). Alteration of lymphocyte subsets was positively correlated with sex, age, smoking, tumor stage and distant metastasis of GC patients (all P<0.05). Follow-up analysis indicated significantly higher DFS for patients with high circulating $CD19^+$ lymphocytes compared to those with low $CD19^+$ lymphocytes (P=0.037), with $CD19^+$ showing an important cutoff of $7.91{\pm}2.98%$ Conclusion: Circulating lymphocyte subsets in GC patients are significantly changed, and elevated CD19+ cells may predict a favorable survival.

• Asian Pacific Journal of Cancer Prevention
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• 제15권2호
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• pp.1023-1029
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• 2014

Background: The purpose of our study was to elucidate the joint effects of combined smoking and alcohol intake on esophageal cancer mortality in Japanese men through a large cohort study with a 20-year follow-up period. Materials and Methods: The Japan Collaborative Cohort Study for Evaluation of Cancer Risk (JACC Study) was established in the late 1980s, including 46,395 men and 64,190 women aged 40 years and older and younger than 80. Follow-up of these participants was conducted until 2009. We used the Cox proportional hazards model to analyze data for 42,408 people excluding female participants, 411 people with histories of malignant neoplasms, and 3,576 with unclear smoking and drinking data. Results: The joint effects of age at start of smoking and amount of alcohol consumed per day were compared with non-smokers and non-drinkers or those consuming less than one unit of alcohol per day. The mortality risk was 9.33 (95% confidence interval, 2.55-34.2) for those who started smoking between ages 10 and 19 years and drinking at least three units of alcohol per day. Regarding the joint effects of cumulative amount of smoking and alcohol intake, the risk was high when both smoking and alcohol intake were above a certain level. Conclusions: In this Japanese cohort study, increased cancer mortality risks were observed, especially for people who both started smoking early and drank alcohol. Quitting smoking or not starting to smoke at any age and reducing alcohol consumption are important for preventing esophageal cancer in Japan.

• Journal of Preventive Medicine and Public Health
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• 제53권5호
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• pp.342-352
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• 2020

Objectives: The aim of this retrospective cohort study was to investigate whether non-alcoholic fatty liver disease (NAFLD) was associated with incident bone mineral density (BMD) decrease. Methods: This study included 4536 subjects with normal BMD at baseline. NAFLD was defined as the presence of fatty liver on abdominal ultrasonography without significant alcohol consumption or other causes. Decreased BMD was defined as a diagnosis of osteopenia, osteoporosis, or BMD below the expected range for the patient's age based on dual-energy X-ray absorptiometry. Cox proportional hazards models were used to estimate the hazard ratio of incident BMD decrease in subjects with or without NAFLD. Subgroup analyses were conducted according to the relevant factors. Results: Across 13 354 person-years of total follow-up, decreased BMD was observed in 606 subjects, corresponding to an incidence of 45.4 cases per 1000 person-years (median follow-up duration, 2.1 years). In the model adjusted for age and sex, the hazard ratio was 0.65 (95% confidence interval, 0.51 to 0.82), and statistical significance disappeared after adjustment for body mass index (BMI) and cardiometabolic factors. In the subgroup analyses, NAFLD was associated with a lower risk of incident BMD decrease in females even after adjustment for confounders. The direction of the effect of NAFLD on the risk of BMD decrease changed depending on BMI category and body fat percentage, although the impact was statistically insignificant. Conclusions: NAFLD had a significant protective effect on BMD in females. However, the effects may vary depending on BMI category or body fat percentage.

• Journal of Korean Medical Science
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• 제33권53호
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• pp.341.1-341.11
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• 2018

Background: The converging epidemics of tuberculosis (TB) and end-stage renal disease (ESRD) have generated a significant public health burden, however, previous studies have been limited to a small number of patients. This nationwide cohort study aimed to assess the rate of developing active TB among patients receiving dialysis for ESRD. Methods: The Korean national health insurance database was used to identify patients receiving dialysis for new-onset ESRD during 2004-2013, who were propensity score matched to an equivalent number of non-dialysis subjects from the general population. The incidences of active TB in the ESRD and control cohorts were calculated for 2004-2013, and multivariable Cox proportional hazards model was used to evaluate the ESRD-related risk of active TB. Results: During 2004-2013, 59,584 patients received dialysis for newly diagnosed ESRD. In the dialysis and control cohorts, 457 (0.8%) and 125 (0.2%) cases of active TB were detected, respectively. Patients with ESRD were associated with a significantly higher risk of active TB compared to the controls (incidence rate ratio, 4.80). The ESRD cohort had an independently elevated risk of active TB (adjusted hazard ratio, 4.39; 95% confidence interval, 3.60-5.37). Conclusion: We found that patients receiving dialysis for ESRD had an elevated risk of active TB. These results highlight the need for detailed and well-organised guidelines for active TB screening among patients with ESRD.

• Korean Journal of Radiology
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• 제22권3호
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• pp.425-434
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• 2021

Objective: To investigate the potential value of ¹⁸F-fluorodeoxyglucose (FDG) PET/CT in predicting the survival of patients with primary tracheal malignant tumors. Materials and Methods: An analysis of FDG PET/CT findings in 37 primary tracheal malignant tumor patients with a median follow-up period of 43.2 months (range, 10.8-143.2 months) was performed. Cox proportional hazards regression analyses were used to assess the associations between quantitative ¹⁸F-FDG PET/CT parameters, other clinic-pathological factors, and overall survival (OS). A risk prognosis model was established according to the independent prognostic factors identified on multivariate analysis. A survival curve determined by the Kaplan-Meier method was used to assess whether the prognosis prediction model could effectively stratify patients with different risks factors. Results: The median survival time of the 37 patients with tracheal tumors was 38.0 months, with a 95% confidence interval of 10.8 to 65.2 months. The 3-year, 5-year and 10-year survival rate were 54.1%, 43.2%, and 16.2%, respectively. The metabolic tumor volume (MTV), total lesion glycolysis (TLG), maximum standardized uptake value, age, pathological type, extension categories, and lymph node stage were included in multivariate analyses. Multivariate analysis showed MTV (p = 0.011), TLG (p = 0.020), pathological type (p = 0.037), and extension categories (p = 0.038) were independent prognostic factors for OS. Additionally, assessment of the survival curve using the Kaplan-Meier method showed that our prognosis prediction model can effectively stratify patients with different risks factors (p < 0.001). Conclusion: This study shows that ¹⁸F-FDG PET/CT can predict the survival of patients with primary tracheal malignant tumors. Patients with an MTV > 5.19, a TLG > 16.94 on PET/CT scans, squamous cell carcinoma, and non-E1 were more likely to have a reduced OS.

• 대한치과보철학회지
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• 제57권4호
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• pp.342-349
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• 2019

목적: 이 연구의 목적은 구치부 영역에서 임플란트 지지 고정 보철물의 재료에 따른 생존율과 성공률을 후향적으로 조사하는 것이다. 또한 임플란트 지지 고정성 보철물에서 발생하는 합병증의 양상을 관찰하고 실패에 영향을 주는 요인을 평가하는 것이다. 대상 및 방법: 2011년 1월부터 2018년 6월 사이에 전북대학교 치과병원 치과보철과에서 한 명의 보철전문의에 의해 구치부 임플란트 보철 수복을 시행한 환자를 대상으로 하였다. 의료기록을 통해 환자의 성별, 연령, 보철물의 재료, 위치, 유형 및 합병증을 조사하였다. 생존율 및 성공률 분석을 위해 Kaplan-Meier 분석법을 이용하였으며, 집단간 비교를 위해 Log-rank test를 사용하였다. 또한 Cox proportional hazards model을 이용하여 위험요소가 성공률에 미치는 영향을 분석하였다. 결과: 총 245명의 환자에서 364개의 임플란트 보철물이 관찰되었으며, 평균 추적관찰기간은 17.1개월이었다. 전체 임플란트 보철물의 3년, 5년 누적생존율은 각각 97.5%, 91.0%로 관찰되었으며, 총 5개의 임플란트 보철물이 실패하여 제거되었다. 임플란트 보철물의 3년, 5년 누적성공률은 각각 61.1%, 32.9%로 관찰되었으며, 재료, 성별, 연령, 보철물의 위치, 유형은 누적성공률에 영향을 미치지 않았다 (P > .05). 합병증은 인접면 접촉 상실 (53건), 유지력 상실 (17건), 임플란트 주위 점막염 (12건), 저위교합 (4건) 등의 순으로 발생하였다. 결론: 구치부에서 임플란트 지지 고정성 보철물의 높은 누적생존율을 고려할 때, 임플란트는 수복 재료와 상관없이 구치부에서 치아를 대체할 수 있는 신뢰할만한 치료방법으로 생각된다. 그러나 합병증이 빈번히 발생하기 때문에 정기적인 검사와 필요한 경우 수리 및 조정이 매우 중요하다.