1.A 10-Gene Signature to Predict the Prognosis of Early-Stage Triple-Negative Breast Cancer
Chang Min KIM ; Kyong Hwa PARK ; Yun Suk YU ; Ju Won KIM ; Jin Young PARK ; Kyunghee PARK ; Jong-Han YU ; Jeong Eon LEE ; Sung Hoon SIM ; Bo Kyoung SEO ; Jin Kyeoung KIM ; Eun Sook LEE ; Yeon Hee PARK ; Sun-Young KONG
Cancer Research and Treatment 2024;56(4):1113-1125
Purpose:
Triple-negative breast cancer (TNBC) is a particularly challenging subtype of breast cancer, with a poorer prognosis compared to other subtypes. Unfortunately, unlike luminal-type cancers, there is no validated biomarker to predict the prognosis of patients with early-stage TNBC. Accurate biomarkers are needed to establish effective therapeutic strategies.
Materials and Methods:
In this study, we analyzed gene expression profiles of tumor samples from 184 TNBC patients (training cohort, n=76; validation cohort, n=108) using RNA sequencing.
Results:
By combining weighted gene expression, we identified a 10-gene signature (DGKH, GADD45B, KLF7, LYST, NR6A1, PYCARD, ROBO1, SLC22A20P, SLC24A3, and SLC45A4) that stratified patients by risk score with high sensitivity (92.31%), specificity (92.06%), and accuracy (92.11%) for invasive disease-free survival. The 10-gene signature was validated in a separate institution cohort and supported by meta-analysis for biological relevance to well-known driving pathways in TNBC. Furthermore, the 10-gene signature was the only independent factor for invasive disease-free survival in multivariate analysis when compared to other potential biomarkers of TNBC molecular subtypes and T-cell receptor β diversity. 10-gene signature also further categorized patients classified as molecular subtypes according to risk scores.
Conclusion
Our novel findings may help address the prognostic challenges in TNBC and the 10-gene signature could serve as a novel biomarker for risk-based patient care.
2.Androgen Receptor as a Predictive Marker for Pathologic Complete Response in Hormone Receptor–Positive and HER-2–Negative Breast Cancer with Neoadjuvant Chemotherapy
Eun-Gyeong LEE ; Dong-Eun LEE ; Hyun hee KIM ; Jai Hong HAN ; Seeyoun LEE ; Han-Sung KANG ; Eun Sook LEE ; Heejung CHAE ; Sung Hoon SIM ; Keun Seok LEE ; Youngmee KWON ; So-Youn JUNG
Cancer Research and Treatment 2023;55(2):542-550
Purpose:
This study investigated pathological complete response (pCR) according to androgen receptor (AR) in breast cancer patients undergoing neoadjuvant chemotherapy and estimated the relationship between AR expression and clinicopathological factors.
Materials and Methods:
We identified 624 breast cancer patients who underwent surgery after neoadjuvant chemotherapy at the National Cancer Center in Goyang, Korea from April 2016 to October 2019. We retrospectively collected the clinicopathologic information and AR expression results and analyzed the data according to cancer stage, hormonal receptor (HR) status, human epidermal growth factor receptor 2 (HER2) status, tumor subtype, and pCR.
Results:
Among the 624 breast cancer patients, 529 (84.8%) were AR-positive (AR+) patients and 95 (15.2%) were AR-negative (AR–) patients. AR+ patients showed more estrogen receptor (ER) positivity, progesterone receptor (PR) positivity, HER2-positivity, and HR-positive and HER2-negative (HR+/HER2–) subtype. The rate of pCR was 31.4% (196/624). AR– patients had a significantly higher rate of pCR than AR+ patients (AR– 43.2% vs. AR+ 29.3%, p=0.007). The tumor factors associated with pCR were early stage, histologic grade 3, ER-negative, PR-negative, AR-negative, HER2-positive, and high Ki-67 values. In univariable analysis, AR+ significantly decreased the state of pCR (odds ratio, 0.546; 95% confidence interval, 0.349 to 0.853; p=0.008). According to tumor subtype, AR– tumor showed higher pCR rate in HR+/HER2– subtype (AR– 28.6% vs. AR+ 7.3%, p=0.022).
Conclusion
AR expression is predominant in the HR+/HER2– subtype. AR– is significantly associated with the pCR rate in breast cancer patients, especially within HR+/HER2– subtype. When determining neoadjuvant chemotherapy for the HR+/HER2– subtype, AR expression can be considered as a pCR predictive marker.
3.Highly water-soluble diacetyl chrysin ameliorates diabetes-associated renal fibrosis and retinal microvascular abnormality in db/db mice
Young-Hee KANG ; Sin-Hye PARK ; Young Eun SIM ; Moon-Sik OH ; Hong Won SUH ; Jae-Yong LEE ; Soon Sung LIM
Nutrition Research and Practice 2023;17(3):421-437
BACKGROUND/OBJECTIVES:
Chronic or intermittent hyperglycemia is associated with the development of diabetic complications. Oxidative stress and inflammation can be altered by hyperglycemia in diverse tissues, including kidneys and eyes, and play a pivotal role in diabetic complications. Our previous studies showed that the water-insoluble 5,7-dihydroxyflvone chrysin effectively combats diabetic damages incurred in diabetic kidneys and retinas. The current study employed the newly-synthesized 5.7-di-O-acetylchrysin, having higher solubility than chrysin, to compare the effects on diabetes-associated renal fibrosis and abnormal retinal neovascularization.MATERIALS/METHODS: In the in vivo study, db/db mice as animal models of type 2 diabetes were orally administrated 10 mg/kg BW diacetylchrysin, daily for 10 weeks.
RESULTS:
Unlike chrysin, oral administration of 10 mg/kg diacetylchrysin did not lower the blood glucose level and 24 h urine volume in db/db mice. Nevertheless, the urinary albumin excretion was markedly reduced. The administration of diacetylchrysin also diminished the deposition of collagen fibers in diabetic glomeruli and tubules by suppressing the induction of connective tissue growth factor and collagen IV in diabetic kidneys. Supplying diacetylchrysin enhanced the membrane type-1 matrix metalloproteinase (MMP) expression reduced in diabetic kidneys, while the tissue inhibitor of MMP-2 induction was attenuated in diacetylchrysin-challenged diabetic kidneys. In addition, supplementing diacetylchrysin to diabetic mice ameliorated renal injury due to glomerulosclerosis and tubular interstitial fibrosis. Furthermore, the reduced retinal inductions of Zonula occludens-1 and vascular endothelial cadherin in db/db mice were elevated in the retinal tissues of diacetylchrysintreated animals. Oral administration of diacetylchrysin curtailed the induction of vascular endothelial growth factor (VEGF) and VEGF receptor 2 in db/db mice, ultimately retarding diabetes-associated retinal neovascularization. Additionally, the retinal formation of acellular capillaries with leaky vessels was reduced in diacetylchrysin-treated db/db mice.
CONCLUSION
Diacetylchrysin may act as a potent pro-health agent for treating renal fibrosisassociated diabetic nephropathy and retinal neovascularization-associated diabetic retinopathy.
4.Impacts of Subtype on Clinical Feature and Outcome of Male Breast Cancer: Multicenter Study in Korea (KCSG BR16-09)
Jieun LEE ; Keun Seok LEE ; Sung Hoon SIM ; Heejung CHAE ; Joohyuk SOHN ; Gun Min KIM ; Kyung-Hee LEE ; Su Hwan KANG ; Kyung Hae JUNG ; Jae-ho JEONG ; Jae Ho BYUN ; Su-Jin KOH ; Kyoung Eun LEE ; Seungtaek LIM ; Hee Jun KIM ; Hye Sung WON ; Hyung Soon PARK ; Guk Jin LEE ; Soojung HONG ; Sun Kyung BAEK ; Soon Il LEE ; Moon Young CHOI ; In Sook WOO
Cancer Research and Treatment 2023;55(1):123-135
Purpose:
The treatment of male breast cancer (MBC) has been extrapolated from female breast cancer (FBC) because of its rarity despite their different clinicopathologic characteristics. We aimed to investigate the distribution of intrinsic subtypes based on immunohistochemistry, their clinical impact, and treatment pattern in clinical practice through a multicenter study in Korea.
Materials and Methods:
We retrospectively analyzed clinical data of 248 MBC patients from 18 institutions across the country from January 1995 to July 2016.
Results:
The median age of MBC patients was 63 years (range, 25 to 102 years). Among 148 intrinsic subtype classified patients, 61 (41.2%), 44 (29.7%), 29 (19.5%), and 14 (9.5%) were luminal A, luminal B, human epidermal growth factor receptor 2, and triple-negative breast cancer, respectively. Luminal A subtype showed trends for superior survival compared to other subtypes. Most hormone receptor-positive patients (166 patients, 82.6%) received adjuvant endocrine treatment. Five-year completion of adjuvant endocrine treatment was associated with superior disease-free survival (DFS) in patients classified with an intrinsic subtype (hazard ratio [HR], 0.15; 95% confidence interval [CI], 0.04 to 0.49; p=0.002) and in all patients (HR, 0.16; 95% CI, 0.05 to 0.54; p=0.003).
Conclusion
Distribution of subtypes of MBC was similar to FBC and luminal type A was most common. Overall survival tended to be improved for luminal A subtype, although there was no statistical significance. Completion of adjuvant endocrine treatment was associated with prolonged DFS in intrinsic subtype classified patients. MBC patients tended to receive less treatment. MBC patients should receive standard treatment according to guidelines as FBC patients.
5.Association between Caregiver’s Awareness of Human Rights and Quality of Service: Focused on Human Right Education
Eun-Sim JEONG ; Young-Joon SEO ; Young-Joo WON ; Min-Hee HEO ; Jin-Won NOH
Health Policy and Management 2023;33(3):311-324
Background:
Long-term care insurance for the elderly has been stably established along with the quantitative expansion of long-term care facilities. Indeed, the need for a paradigm about human rights-based service approach is being raised throughout society from a service perspective. Therefore, this study aimed to analyze the association between elderly human rights awareness and quality of service by considering human rights education as a moderate variable.
Methods:
This study conducted surveys with 138 caregivers working in long-term care facilities located in Seoul and Gangwon.General characteristics, awareness of human rights, and the level of service quality were examined using descriptive statistics, frequency analysis, and correlation analysis. And multi-variable linear regression with a hierarchical framework was employed. These analyses were performed using IBM SPSS ver. 25.0.
Results:
Of the 138 caregivers, 97.1% were female, 87.7% were more than 50 years old, and most of their education level was high-school graduates. Their length of employment ranged from more than 5 years to less than 10 years. The level of awareness regarding elderly human rights of the elderly was below normal (mean=2.21), but the quality of service was high (mean=4.21), and the need for human rights education was also high (mean=4.28). Among the general characteristics, the length of employment was significantly associated with awareness of elderly human rights. Moreover, political rights awareness, included as sub-domains of human rights, was positively associated with quality of service. However, the moderating variable, human rights education, was not significantly associated with the quality of service.
Conclusion
In this study, human rights education, as a moderating variable, did not have a statistically significant effect on caregivers’ human rights awareness in relation to service quality. This finding is inconsistent with previous research results. These results can be explained by the fact that the frequency of education in long-term care facilities was a significant factor in the practice of protecting the human rights of the elderly. Therefore ongoing encouragement for the frequency of current human rights education and improvements in the educational approach appear to be necessary. In addition, these findings reveal the need for strength of education policies and effective in-depth research about human rights and quality of service to respect the human rights of the elderly.
6.Effects of Hospital Ethical Climate and Communication Self-Efficacy on Nursing Cares Left Undone among Nurses
Yoon Goo NOH ; Bong Hee SIM ; Eun Su LEE
Korean Journal of Occupational Health Nursing 2023;32(1):20-29
Purpose:
This study aimed to identify the effects of hospital ethical climate and communication self-efficacy on nursing care left undone.
Methods:
The participants were 142 nurses working in a general hospital. Data were collected from July 18 to August 30, 2021. Data were analyzed by t-test, ANOVA, Pearson correlation, and multiple regression analysis using the SPSS/WIN 25.0 program.
Results:
(a) The mean value of hospital ethical climate was 3.54±0.41, communication self-efficacy was 5.03±0.81, and the sum of nursing cares left undone was 3.68±3.14.(b) Nursing cares left undone had a negative correlation with hospital ethical climate(r=-.25, p=.003) but not with communication self-efficacy (r=-.13,p=.116). (c) Factors that affected nursing cares left undone included education (≥master) (β=.23, p=.005), marital status (single) (β=-.19, p=.018), age (26~27) (β=-.18, p=.022), and hospital ethical climate (β=-.18, p=.029); the explanation power was 18.0% (F=8.66, p<.001).
Conclusion
Our study shows that hospital ethical climate plays a significant role in nursing cares left undone of nurses. It is important to strengthen hospital ethical climate to lower the incidence of nursing cares left undone. These results may serve as basic data to help develop strategies for reducing the incidence of nursing cares left undone.
7.Purple perilla frutescens extracts containing α-asarone inhibit inflammatory atheroma formation and promote hepatic HDL cholesterol uptake in dyslipidemic apoE-deficient mice
Sin-Hye PARK ; Young Eun SIM ; Min-Kyung KANG ; Dong Yeon KIM ; Il-Jun KANG ; Soon Sung LIM ; Young-Hee KANG
Nutrition Research and Practice 2023;17(6):1099-1112
BACKGROUND/OBJECTIVES:
Dyslipidemia causes metabolic disorders such as atherosclerosis and fatty liver syndrome due to abnormally high blood lipids. Purple perilla frutescens extract (PPE) possesses various bioactive compounds such as α-asarone, chlorogenic acid and rosmarinic acid. This study examined whether PPE and α-asarone improved dyslipidemia-associated inflammation and inhibited atheroma formation in apolipoprotein E (apoE)-deficient mice, an experimental animal model of atherosclerosis.MATERIALS/METHODS: ApoE-deficient mice were fed on high cholesterol-diet (Paigen’s diet) and orally administrated with 10–20 mg/kg PPE and α-asarone for 10 wk.
RESULTS:
The Paigen’s diet reduced body weight gain in apoE-deficient mice, which was not restored by PPE or α-asarone. PPE or α-asarone improved the plasma lipid profiles in Paigen’s diet-fed apoE-deficient mice, and despite a small increase in high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein (LDL)-cholesterol, and very LDL were significantly reduced. Paigen’s diet-induced systemic inflammation was reduced in PPE or α-asarone-treated apoE-deficient mice. Supplying PPE or α-asarone to mice lacking apoE suppressed aorta atherogenesis induced by atherogenic diet. PPE or α-asarone diminished aorta accumulation of CD68- and/or F4/80-positive macrophages induced by atherogenic diet in apoE-deficient mice. Treatment of apoE-deficient mice with PPE and α-asarone resulted in a significant decrease in plasma cholesteryl ester transfer protein level and an increase in lecithin:cholesterol acyltransferase reduced by supply of Paigen’s diet. Supplementation of PPE and α-asarone enhanced the transcription of hepatic apoA1 and SR-B1 reduced by Paigen’s diet in apoE-deficient mice.
CONCLUSIONS
α-Asarone in PPE inhibited inflammation-associated atheroma formation and promoted hepatic HDL-C trafficking in dyslipidemic mice.
8.Ten-Year Trends of Hepatitis A Seroprevalence in People Living with HIV in Korea
Shinwon LEE ; Jeong Eun LEE ; Soon Ok LEE ; Yong Ki SIM ; Sun Hee LEE
Infection and Chemotherapy 2022;54(3):529-533
Epidemiological information on hepatitis A among people living with HIV (PLHIV) in Korea is scarce. This retrospective study was performed at a tertiary care hospital and included 756 PLHIV with anti- hepatitis A virus (HAV) IgG tests. Between 2012 and 2021, the age at antiHAV IgG seroconversion is gradually delayed, and the proportion of individuals susceptible to HAV infection increased among adult PLHIV in Korea. The independent risk factors for HAV seropositivity were female sex and HBs antigen (Ag) positivity. Therefore, HAV vaccination is highly recommended for young PLHIV, especially for women or HBsAg-positive individuals.
9.Impact of Pediatric Alopecia Areata on Quality of Life of Patients and Their Family Members: A Nationwide Multicenter Questionnaire Study
Jee Woong CHOI ; Yul Hee KIM ; Hyunbin KWAK ; Jin PARK ; Won-Soo LEE ; Hoon KANG ; Jung Eun KIM ; Tae-Young YOON ; Ki-Ho KIM ; Yong Hyun JANG ; Do Won KIM ; Moon-Bum KIM ; Bark-Lynn LEW ; Woo-Young SIM ; Jiehyun JEON ; Soo Hong SEO ; Ohsang KWON ; Chang-Hun HUH ; Dong-Youn LEE ; Yang Won LEE ; Byung Choel PARK ; Chong Hyun WON ; Do Young KIM ; Hyojin KIM ; Beom Joon KIM ; Young LEE ; Sang Seok KIM ; Gwang Seong CHOI ; The Korean Hair Research Society
Annals of Dermatology 2022;34(4):237-244
Background:
Pediatric alopecia areata (AA) can affect the quality of life (QoL) of patients and their family members. Research on the QoL and burden on family members in pediatric AA is limited.
Objective:
This nationwide multicenter questionnaire study described the QoL and burden of the family members of patients with pediatric AA.
Methods:
This nationwide multicenter questionnaire study enrolled AA patients between the ages of 5 and 18 years from March 1, 2017 to February 28, 2018. Enrolled patients and their parents completed the modified Children’s Dermatology Life Quality Index (CDLQI) and the modified Dermatitis Family Impact (mDFI). The disease severity was measured using the Severity of Alopecia Tool (SALT) survey scores.
Results:
A total of 268 patients with AA from 22 hospitals participated in this study. Our study found that the efficacy and satisfaction of previous treatments of AA decreased as the severity of the disease increased. The use of home-based therapies and traditional medicines increased with the increasing severity of the disease, but the efficacy felt by patients was limited. CDLQI and mDFI scores were higher in patients with extensive AA than those with mild to moderate AA. The economic and time burden of the family members also increased as the severity of the disease increased.
Conclusion
The severity of the AA is indirectly proportional to the QoL of patients and their family members and directly proportional to the burden. Physicians need to understand these characteristics of pediatric AA and provide appropriate intervention to patients and their family members.
10.Risk Prediction Model Based on Magnetic Resonance Elastography-Assessed Liver Stiffness for Predicting Posthepatectomy Liver Failure in Patients with Hepatocellular Carcinoma
Hyo Jung CHO ; Young Hwan AHN ; Min Suh SIM ; Jung Woo EUN ; Soon Sun KIM ; Bong Wan KIM ; Jimi HUH ; Jei Hee LEE ; Jai Keun KIM ; Buil LEE ; Jae Youn CHEONG ; Bohyun KIM
Gut and Liver 2022;16(2):277-289
Background/Aims:
Posthepatectomy liver failure (PHLF) is a major complication that increases mortality in patients with hepatocellular carcinoma after surgical resection. The aim of this retrospective study was to evaluate the utility of magnetic resonance elastography-assessed liver stiffness (MRE-LS) for the prediction of PHLF and to develop an MRE-LS-based risk prediction model.
Methods:
A total of 160 hepatocellular carcinoma patients who underwent surgical resection with available preoperative MRE-LS data were enrolled. Clinical and laboratory parameters were collected from medical records. Logistic regression analyses were conducted to identify the risk factors for PHLF and develop a risk prediction model.
Results:
PHLF was present in 24 patients (15%). In the multivariate logistic analysis, high MRE-LS (kPa; odds ratio [OR] 1.49, 95% confidence interval [CI] 1.12 to 1.98, p=0.006), low serum albumin (≤3.8 g/dL; OR 15.89, 95% CI 2.41 to 104.82, p=0.004), major hepatic resection (OR 4.16, 95% CI 1.40 to 12.38, p=0.014), higher albumin-bilirubin score (>–0.55; OR 3.72, 95% CI 1.15 to 12.04, p=0.028), and higher serum α-fetoprotein (>100 ng/mL; OR 3.53, 95% CI 1.20 to 10.40, p=0.022) were identified as independent risk factors for PHLF. A risk prediction model for PHLF was established using the multivariate logistic regression equation. The area under the receiver operating characteristic curve (AUC) of the risk prediction model was 0.877 for predicting PHLF and 0.923 for predicting grade B and C PHLF. In leave-one-out cross-validation, the risk model showed good performance, with AUCs of 0.807 for all-grade PHLF and 0. 871 for grade B and C PHLF.
Conclusions
Our novel MRE-LS-based risk model had excellent performance in predicting PHLF, especially grade B and C PHLF.

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