개 유선 종양 세포에서 TSG-6와 HIF1a의 역할

학위논문(석사) -- 서울대학교대학원 : 수의과대학 수의학과, 2023. 2. 윤화영 .HIF1a-induced hypoxia is a major characteristic of solid tumors that plays an important role in cancer growth, metastasis, and chronic inflammation. Tumor necrosis factor (TNF) stimulated gene (TSG)-6 is a strong regulator of anti-inflammatory pathways, but its role in cancer cells remains unclear. We hypothesized that hypoxia up-regulates TSG-6, thereby increasing the metastatic and growth potential of cancer cells. Primary and metastatic canine mammary gland tumor (MGT) cell lines (CIPp and CIPm) were transfected with TSG-6 specific siRNA and treated with cobalt chloride (CoCl2) for 48 h to chemically induce a hypoxia environment. The expression of hypoxia-inducible factor-1-alpha (HIF1a) was evaluated by RT-qPCR and western blot analysis. The metastatic ability of cancer cells and cell cycle distribution were assessed with extracellular matrix invasion assays and flow cytometry. HIF1a up-regulation, induced by CoCl2, was significantly inhibited in the TSG-6-knockdown group in both canine MGT cell lines. The change in the expression levels of HIF1a corresponded to the change of invading cells in the TSG-6-knockdown group. TSG-6-knockdown in the hypoxia group showed decreased proliferation, associated with G2/M phase arrest. HIF1a expression in hypoxic condition is regulated by TSG-6 expression in canine MGT. TSG-6-knockdown causes down-regulation of HIF1a, thereby reducing the metastatic and proliferative abilities of cancer cells. TSG-6 in canine MGT has a potential as a therapeutic target in anti-cancer therapy.개의 유선 종양은 암컷 개에서 가장 호발하는 고형 종양으로 알려져 있다. 저산소증 유발 인자-1-알파(HIF1a) 에 의한 저산소증은 암 성장, 전이, 만성 염증에 중요한 역할을 하는 고형 종양의 주요 특징이다. 종양 괴사 인자(TNF) 자극 유전자(TSG)-6은 항염증 경로의 강력한 조절자이지만 암세포에서의 역할은 아직 불분명하다. 우리는 저산소증이 TSG-6을 상향 조절하여 암세포의 전이 및 성장 잠재력을 증가시킨다는 가설을 세웠다. 원발성 및 전이성 개 유선 종양 세포주(CIPp 및 CIPm)를 TSG-6 특이적 siRNA로 발현을 약화시키고 염화 코발트(CoCl2)로 48시간 동안 처리하여 화학적으로 저산소증 환경을 유도했다. HIF1a의 발현은 RT-qPCR 및 western blot 분석을 통해 평가하였다. 암세포의 전이 능력 및 세포 주기 분포는 세포외 기질 침습 분석 및 유세포 분석으로 평가하였다. CoCl2에 의해 유도된 HIF1α 상향 조절은 두 개의 세포주 (CIPp, CIPm)에서 확인되었으나 TSG-6 발현 약화 그룹에서 유의미하게 억제되었다 (CIPp 51.9% 감소, p < 0.05; CIPm 37.6% 감소, p < 0.01). HIF1a의 발현 수준의 변화는 TSG-6 발현 약화 그룹에서 침입 세포의 변화에 상응하였다 (CIPp 58.7% 감소, p < 0.01; CIPm 69.5% 감소, p < 0.001). 저산소증 그룹의 TSG-6 발현 약화는 G2/M 주기 정지와 관련하여 증식이 감소하는 것을 보여주었다. 저산소 상태에서 HIF1a 발현은 개 유선 종양 세포주에서 TSG-6 발현에 의해 조절된다. TSG-6 발현 약화는 HIF1a의 하향 조절을 유발하여 암세포의 전이 및 증식 능력을 감소시킨다. 그러므로 개 유선 종양 세포의 TSG-6은 항암 요법의 치료 표적으로 고려할 수 있는 잠재력이 있다.1. Introduction 1 2. Materials and Methods 3 2.1. Cell lines and cultures 3 2.2. Cobalt chloride treatment 3 2.3. Transfection with small interfering RNA (siRNA) 4 2.4. Cell viability assay 4 2.5. RNA extraction, cDNA synthesis, quantitative real time PCR (RT-qPCR) 4 2.6. Protein extraction and western blot 5 2.7. Invasion assay 6 2.8. Cell cycle assay 6 2.9. Statistical analysis 7 3. Results 9 3.1. Cell viability analysis of mammary gland tumors when using CoCl2 9 3.2. Expression of TSG-6 in tumor cells under hypoxic conditions 9 3.3. Relationship between TSG-6 and HIF1 in tumor cells 10 3.4. Hypoxia increases the metastatic capability of the CIPp and CIPm cell lines but not in the TSG-6-knockdown groups 10 3.5. Cell cycle features were affected in TSG-6-knockdown CIPp 10 4. Discussion 12 5. References 23 국문 초록 29석

Association of employment status and income with self-rated health among waged workers with disabilities in South Korea: population-based panel study

OBJECTIVE: This study aimed to examine the association of employment status and income with self-rated health among waged workers with disabilities in South Korea. METHODS: This study used the Panel Survey of Employment for the Disabled from 2011 to 2015. A total of 951 waged workers with disabilities were selected as baseline subjects in 2011 and were followed up for 5 years. This study used a generalised linear mixed model after adjusting for covariates. RESULTS: Among 951 waged workers with disabilities, the results showed that 39.3% of workers with disabilities reported poor self-rated health. Workers with disabilities with a precarious employment status and lower income were 1.22 (95% CI 1.21 to 1.23) and 1.81 (95% CI 1.80 to 1.83) times more likely to have poor self-rated health than those with permanent employment and higher income, respectively. A subgroup analysis found that precarious workers with disabilities in lower income households had higher possibilities of poor self-rated health. CONCLUSION: This study suggests that precarious employment and lower income of waged workers with disabilities are significantly associated with poor self-rated health compared with those with permanent jobs or higher income.ope

일개 대학병원 외래환자의 예약부도(No-Show) 관련요인

Objective: This study examines factors associated with no-show in an academic medical center in Korea. Methods: Electronic data regarding medical appointment during one academic year (2013.03~2014.02) were derived from a major academic medical center in Seoul. Medical appointment was divided into two groups (i.e., consultation vs. test, treatment, and surgery). Comparisons between patients who did show up and those who failed to show up (no-show) were made. A multiple logistic regression was run to estimate factors that are significantly associated with no-show. Results: The results show that overall no-show rate was 5.0%, but the rate of the appointment for test, treatment, and surgery (8.0%) is higher than that of consultation (4.7%). In general, patients aged less than 18 and carrying Medical Aid had higher odds of no-show. Afternoon appointments and Saturday appointments also had higher odds of no-show. In addition, those who had appointments with the Department of Ophthalmology and Department of Otolaryngology and those who made appointments with instructors or residents had higher odds of no-show. Also, slightly different results were found for the two different groups of medical appointment. Conclusion: The results of this study can be used for setting priority for no-show management based on identifying significant no-show predictors. It is important for hospitals to develop more tailored no-show management approaches for consultation, test, treatment, and surgery, respectively, given that the results are somewhat different by the medical appointment type. In addition, it is recommended that future research incorporate qualitative information about the reasons of no-show.ope

Reasons for Surgery Cancellation in a General Hospital: A 10-year Study

Background: This study researched related causes that make scheduled surgeries canceled not to be conducted and based on the research it is to derive issues in order to reduce surgery cancellation. Methods: We analyzed the association of surgery cancellation with patient characteristics, surgical characteristics and surgery schedule related characteristics, using electronic medical record (EMR) data on surgeries conducted at a university hospital in Korea over 10 years. Additionally, we examined the reasons for surgery cancellation based on patient and hospital characteristics. We used chi-square tests to analyze the distribution of various characteristics according to reasons for surgery cancellation. Multivariate logistic regression analyses were conducted to evaluate the factors associated with surgery cancellation. Results: Among 60,333 cases, surgery cancellation rate was 8.0%. The results of the logistic regression indicated a high probability of surgery cancellation when the patient was too old (odds ratio [OR]: 1.35, 95% confidence interval [CI]: 1.14⁻1.59), when it was a neurosurgery case (OR: 1.39, 95% CI: 1.21⁻1.59), when local anesthesia was used (OR: 1.15, 95% CI: 1.07⁻1.24) or when it was a planned surgery (OR: 2.45, 95% CI: 2.21⁻2.73). The surgery cancellation rate was lower when the patient was female (OR: 0.87, 95% CI: 0.82⁻0.93) or when the surgery was related to Obstetrics & Gynecology (OR: 0.53, 95% CI: 0.46⁻0.60) or Ophthalmology (OR: 0.66, 95% CI: 0.56⁻0.79). Among the canceled 4834 cases, the surgery cancellation rate for the reasons of patients was 93.2% and the surgery cancellation rate for the reasons of a hospital was 6.8%. Conclusions: This study found that there are related various causes to cancel operations, including patient characteristics, surgery related characteristics and surgery schedule related characteristics and it means that it would be possible for some reasons to be prevented. Every medical institution should consider the operation cancellation as an important issue and systematic monitoring should be needed.ope

Association between arthritis and socio-demographic factors in Korean elderlies : the National Survey of Korean Elderly (2014, 2017) dataset analysis

Background: As South Korea is becoming an aged society very rapidly, the increase in osteoarthritis prevalence raises various public health issues in this country. This study aimed to explore the socio-demographic factors associated with osteoarthritis in the current Korean elderlies. Methods: Using the National Survey of Korean Elderly data (2014, 2017), we analyzed 20,326 elderlies (males, 8,248; females, 12,078) and conducted multivariate logistic regression analyses by sex. The dependent variable is whether a participant was diagnosed with osteoarthritis or not. Independent variables of interest is socio-demographic factors such as age, marital status, household type, residential area, household income, religion, the longest job, the number of close relatives, the number of close friends, and survey year. Control variables are various health behavioral factors and disease-related factors. Results: Prevalence of osteoarthritis was 19.2% in male elderlies and 47.0% in female elderlies. According to the results of the multivariate logistic regression adjusted for all studied control variables, the odds ratio (OR) for having osteoarthritis of under-elementary school graduates (their counterpart was college graduate group) was 1.81 (95% confidence interval [CI], 1.29– 2.52) in males and 1.67 (95% CI, 1.12–2.47) in females. The OR of those having a job in agriculture & forestry fishery as their longest job (their counterpart was those who had never participated in labor force during their lifetime) was 5.07 (95% CI, 1.46–17.58) in males and 1.49 (95% CI, 1.27–1.74) in females. In males, the second-low quartile group in household yearly income (their counterpart was the highest quartile group) had the OR of 1.22 (95% CI, 0.98–1.53). In females, the OR of those having a religion of Buddhism (their counterpart was those having no religion) was 1.20 (95% CI, 1.07–1.35) and the OR of those who had no relatives (their counterpart was those having more than 3 close relatives) was 1.31 (95% CI, 1.10–1.56). Conclusion: This study found that in Korean elderlies, education, the longest job, household income, religion, and the number of close relatives are associated with their suffering from osteoarthritis. Further study and designing appropriate interventions are needed to alleviate current and future individual and socioeconomic burdens of osteoarthritis in an aged society like South Korea.ope

Factors Associated with Health Check-up and Cancer Screening Participation among Family Caregivers of Patients with Dementia: A Cross-Sectional Study

Background: Providing care for patients with dementia can negatively influence the physical health and health behaviours of family caregivers. A better understanding of the factors associated with health check-up and cancer screening participation is vital for developing effective interventions. Thus, this study aimed to identify factors associated with health check-up and cancer screening participation among family caregivers of patients with dementia. Methods: This was a cross-sectional study that analysed the data of 2,414 family caregivers of patients with dementia collected by the Korea Community Health Survey in 2017. A binomial logistic regression analysis was performed to identify demographic, socioeconomic, and health status factors associated with health check-up and cancer screening participation among family caregivers of patients with dementia. Results: Health check-up and cancer screening rates among family caregivers of patients with dementia were 68.7% and 61.4%, respectively, which were significantly lower than the rates for individuals who were not caregivers of patients with dementia. Those with lower education levels had lower odds ratios (OR) for both health check-up (OR: 0.60) and cancer screening (OR: 0.59) participation. In addition, symptoms of depression were associated with lower participation (health check-up OR: 0.67; cancer screening OR: 0.65). Conclusions: More targeted disease prevention and management strategies must be developed for family caregivers of patients with dementia, particularly those with depressive symptoms and lower education levels.ope

Effect of Number of Household Members on Falls among Disabled Older People

Objectives: To investigate the effect of the number of cohabitating household members on falls among an disabled aging Korean population. Methods: We used data from the first to the fourth waves of the Korea Longitudinal Study of Aging. Using the first wave at baseline, data included 1414 individuals aged 45 years and older who needed assistance for performance of activities of daily living (ADL) or instrumental activities of daily living (IADL). We classified falls as overall falls, falls requiring medical treatment, and hip fractures caused by falls. The number of cohabitating family members was classified as none (living alone), one, two, or more. A generalized estimating equation with logit link was used to examine the association between the number of cohabitating household members with overall falls and injuries caused by falls. Results: Compared to living with two or more household members, living alone was associated with higher odds of overall falls, falls needing medical treatment, and hip fractures caused by falls (odds ratio (OR) 2.13, 95% confidence interval [CI] 1.36-3.34; OR 2.13, 95% CI 1.28-3.53; OR 1.93, 95% CI 1.01-3.69, respectively). These associations were particularly strong in individuals with cognitive decline. Conclusions Living alone is associated with higher odds of overall falls, falls needing medical treatment, and hip fractures caused by falls, particularly for those with cognitive decline. Conclusions: Intervention programs to prevent falls in disabled, aging adults, especially those living alone and those with declined cognitive function, need to provide home care services and promote the use of safety equipment.ope

Risk of Hypertension and Type 2 Diabetes in Relation to Changes in Alcohol Consumption: A Nationwide Cohort Study

Little is known about the risk of hypertension and type 2 diabetes in relation to changes in frequency and amount of alcohol consumption. This study investigated associations between changes in alcohol consumption and the risk of both conditions. This study included 96,129 individuals without hypertension and/or diabetes mellitus aged ≥ 20 years between 2006 and 2008, with follow-up until 31 December 2015. This study identified 29,043 and 18,784 incident cases of hypertension and type 2 diabetes, respectively, during an average follow-up period of 6.2 ± 2.6 and 6.9 ± 1.9 years. This study measured changes in frequency and amount of alcohol consumption using standardized self-administered questionnaires over approximately 2 years. Hazard ratio (HR) and 95% confidence interval (CI) were calculated for the respective risks of the two conditions. Repeated occasional or frequent binge drinking was associated with an increased risk of hypertension (HR: 1.16 or 1.32; 95% CI: 1.11, 1.21 or 1.16, 1.51) and type 2 diabetes (HR: 1.14 or 1.36; 95% CI: 1.09, 1.20 or 1.17, 1.58) compared with continuous nondrinking. Reductions as well as increases in frequency of alcohol consumption among binge drinkers were associated with higher hypertension (HR: 1.29 or 1.30; 95% CI: 1.11, 1.49 or 1.13, 1.49) and type 2 diabetes (HR: 1.26 or 1.56; 95% CI: 1.06, 1.49 or 1.34, 1.81) risk. This study demonstrated that repeated binge drinking, even with a reduction of weekly alcohol consumption frequency, was associated with a higher risk of hypertension and type 2 diabetes.ope

Anemia and incidence of dementia in patients with new-onset type 2 diabetes: a nationwide population-based cohort study

Introduction: This study aimed to examine the association between anemia and the incidence of dementia in patients with new-onset type 2 diabetes. Research design and methods: This study used the Korean National Health Insurance Service-Health Screening Cohort and included 32 590 participants aged ≥40 years who were diagnosed with new-onset type 2 diabetes between 2004 and 2007 and followed up until 2013. Anemia was defined according to the criteria provided by the WHO, hemoglobin <120 g/L for women and <130 g/L for men, and was measured from after diagnosis date of type 2 diabetes to 2007. Dementia was defined by the Classification of Diseases 10th revision code as primary diagnosis and was measured from after hemoglobin measurement to 2013. We calculated the adjusted HR (AHR) and 95% CI to assess the risk of dementia using multivariable Cox proportional hazards regression models. Results: We identified 1682 patients who developed dementia within a 7.5-year follow-up. Among patients with type 2 diabetes, patients with anemia were associated with an increased risk of dementia than those without anemia (AHR, 1.21; 95% CI 1.06 to 1.39). Patients with mild (AHR, 1.18; 95% CI 1.03 to 1.38) and moderate (AHR, 1.39; 95% CI 1.06 to 1.83) anemia were associated with an increased risk of dementia than those without anemia among patients with type 2 diabetes. Men (AHR, 1.47; 95% CI 1.16 to 1.83) and middle-aged adults (AHR, 1.31; 95% CI 1.03 to 1.75) with anemia were associated with an increased risk of dementia than their counterparts without anemia among patients with type 2 diabetes. Conclusions: Our findings suggest that anemia is significantly associated with an increased risk of dementia among patients with newly diagnosed type 2 diabetes.ope

The Effect of Neighborhood Deprivation on Mortality in Newly Diagnosed Diabetes Patients: A Countrywide Population-Based Korean Retrospective Cohort Study, 2002-2013

Background: Neighborhood environmental factors along with individual factors are beginning to make a mark as factors which influence individual health outcomes. The goal of this study is to look at the combined impact of individual and neighborhood socioeconomic status on all-cause mortality in diabetic patients who have just been diagnosed. Methods: The Korean National Health Insurance (2002-2013) was employed in this cohort research, which used a stratified random sample. During the years 2003-2006, a total of 15,882 individuals who were newly diagnosed with diabetes and using oral disease-controlling medication were included in the study. Individual income and neighborhood deprivation index were used to examine the combined effect on all-cause mortality. The frailty model was performed using Cox's proportional hazard regression. Results: During the study period, 28.3 percent (n = 4493) of the 15,882 eligible individuals died. In a Cox regression analysis after adjusting for all covariates, with advantaged and disadvantaged neighborhoods classified according to individual household income, the adjusted HR for patients living in a disadvantaged area was higher compared to patients living in an advantaged area in patients with middle income, compared to the reference group (a high income within an advantaged neighborhood) (HR, 1.22; 95% CI, 1.09-1.35; HR, 1.13; 95% CI, 1.02-1.25, respectively). The adjusted HR for patients with low income who lived in a disadvantaged location was greater than for patients who lived in an advantaged area (HR, 1.34; 95% CI, 1.18-1.53 vs. HR, 1.28; 95% CI, 1.14-1.49). Conclusions: Individual SES has a greater impact on all-cause mortality among diabetic patients when they live in a low-income neighborhood.ope