1.Differential expression of ORAI channels and STIM proteins in renal cell carcinoma subtypes: implications for metastasis and therapeutic targeting
Ji-Hee KIM ; Kyu-Hee HWANG ; Jiyeon OH ; Sung-Eun KIM ; Mi-Young LEE ; Tae Sic LEE ; Seung-Kuy CHA
The Korean Journal of Physiology and Pharmacology 2025;29(1):33-43
Renal cell carcinoma (RCC) presents significant clinical challenges, highlighting the importance of understanding its molecular mechanisms. While store-operated Ca2+ entry (SOCE) is known to play an essential role in tumorigenesis and metastasis, its specific implications across various RCC subtypes remain underexplored.This study analyzed SOCE-related mRNA profiles from the KIRC and KIRP projects in The Cancer Genome Atlas (TCGA) database, focusing on differential gene expression and overall survival outcomes. Functional studies in clear cell RCC (Caki-1) and papillary RCC cell lines (pRCC, Caki-2) revealed increased expression of Orai1 and Orai3, along with STIM1, exhibited in both subtypes, with decreased STIM2 and increased Orai2 expression in pRCC. Notably, Orai3 expression had a gender-specific impact on survival, particularly in females with pRCC, where it inversely correlated with STIM2 expression. Functional assays showed Orai3 dominance in Caki-2 and Orai1 in Caki-1. Interestingly, 2-APB inhibited SOCE in Caki-1 but enhanced it in Caki-2, suggesting Orai3 as the primary SOCE channel in pRCC. Knockdown of Orai1 and Orai3 reduced cell migration and proliferation via regulating focal adhesion kinase (FAK) and Cyclin D1 in both cell lines. These findings highlight the critical roles of Orai1 and Orai3 in RCC metastasis, with Orai3 linked to poorer prognosis in females with pRCC. This study offers valuable insights into RCC diagnostics and potential therapeutic strategies targeting ORAI channels and STIM proteins.
2.Higher Physical Activity is Associated with Reduced Lower Urinary Tract Symptoms in Korean Men
Seo Eun HWANG ; Jae Moon YUN ; Su Hwan CHO ; Kyungha MIN ; Ji Young KIM ; Hyuktae KWON ; Jin Ho PARK
The World Journal of Men's Health 2025;43(1):166-173
Purpose:
Identifying and managing risk factors for lower urinary tract symptoms (LUTS) is crucial because it impacts the quality of life of elderly individuals. Lifestyle factors, including physical activity (PA), and their relationship with LUTS have not been well studied. This objective of this study was to investigate the association between PA and LUTS.
Materials and Methods:
A total of 7,296 men were included in this cross-sectional study. PA was quantified in metabolic equivalent (MET)-hours per week, and LUTS severity was assessed using the international prostate symptom score. Logistic regression was used to analyze the association between PA and LUTS, including voiding and storage symptoms.
Results:
The average age of the participants was 57.8 years, and the prevalence of LUTS was 41.3%. After adjusting for potential confounders, PA was inversely associated with the prevalence and severity of moderate-to-severe LUTS, showing a dose-response pattern (all p for trend <0.01). Compared to the minimal activity group, which engaged in <5 MET-hours per week of PA, the odds ratios for moderate to severe LUTS were 0.83 (95% confidence interval [CI]: 0.72–0.97) for men engaging in 15–30 MET-hours per week, 0.82 (95% CI: 0.71–0.95) for 30–60 MET-hours per week, and 0.72 (95% CI: 0.62–0.84) for ≥60 MET-hours per week. The possible protective effect of PA was still observed in the additional analysis for voiding and storage symptoms showing the same dose-response pattern (all p for trend <0.01).
Conclusions
A higher PA level was associated with a lower prevalence and severity of total, voiding, and storage LUTS in a dose-dependent manner in Korean men.
3.Comparison of Anticancer Effects of Histone Deacetylase Inhibitors CG-745 and Suberoylanilide Hydroxamic Acid in Non-small Cell Lung Cancer
Hyo Jin KIM ; Ui Ri AN ; Han Jee YOON ; Hyun LIM ; Ki Eun HWANG ; Young Suk KIM ; Hak Ryul KIM
Tuberculosis and Respiratory Diseases 2025;88(2):342-352
Background:
Histone deacetylase (HDAC) inhibition offers potential anticancer effects across diverse cancers due to HDAC's significant role in cancer development and progression. Consequently, we demonstrated the therapeutic efficacy of the novel HDAC inhibitor, CG-745, in comparison with existing inhibitors such as suberoylanilide hydroxamic acid (SAHA) in non-small cell lung cancer (NSCLC) cells.
Methods:
CG-745's effect on apoptosis and reactive oxygen species (ROS)-dependent mitochondrial dysfunction was investigated using annexin V assay, MitoSoX, and Western blot in human A549 and H460 cells. Additionally, HDAC expression was analyzed through real-time polymerase chain reaction. We also evaluated the inhibitory effect of CG-745 on epithelial-mesenchymal transition (EMT) induced by transforming growth factor β1 (TGF-β1) via Western blot, scratch analysis, and matrigel invasion analysis.
Results:
Compared to SAHA, CG-745 inhibited cell viability and mRNA expression of HDACs such as HDAC1, HDAC2, HDAC3, and HDAC8. It also induced apoptosis, ROS, and mitochondrial dysfunction in a concentration-dependent manner. CG-745 reversed EMT triggered by TGF-β1 in A549 and H460 cells, and curtailed the migration and invasion enhanced by TGF-β1. CG-745 has demonstrably inhibited EMT and induced apoptosis in NSCLC cells.
Conclusion
CG-745 may represent a novel therapeutic strategy for NSCLC treatment.
4.Novel non-invasive and quantitative assessment of the renal function of transplanted kidneys using Doppler ultrasonography with the vascular index of superb microvascular imaging
Sung Hwan BAE ; Eun Ji LEE ; Jiyoung HWANG ; Seong Sook HONG ; Yun-Woo CHANG ; Boda NAM
Ultrasonography 2025;44(2):160-169
Purpose:
This study assessed the reproducibility and clinical value of the vascular index (VI), derived from superb microvascular imaging (SMI) using Doppler ultrasonography, for evaluating renal function in transplanted kidneys.
Methods:
This retrospective study included 63 renal transplant patients who underwent grayscale and Doppler ultrasonography with SMI from January 2022 to February 2023. The VI of the transplanted kidneys was measured using three methods (VIbox, VIF1, VIF2). The VI was compared across chronic kidney disease (CKD) groups categorized by estimated glomerular filtration rate (eGFR) and Kidney Disease: Improving Global Outcomes (KDIGO) CKD risk groups based on eGFR and albuminuria. The correlation between VI and renal function was evaluated. Univariate and multivariate linear regression analyses were used to identify predictors of eGFR.
Results:
Significant differences in VI were observed among CKD groups based on eGFR (VIbox, P=0.001; VIF1, P<0.001; VIF2, P<0.001) and KDIGO CKD groups based on eGFR and albuminuria (VIbox, P=0.039; VIF1, P=0.001; VIF2, P<0.001). VIF1 and VIF2 demonstrated moderate/high correlations with eGFR (r=0.627, P<0.001 and r=0.657, P<0.001, respectively) and serum creatinine (r=-0.626, P<0.001 and r=-0.649, P<0.001, respectively). VIbox moderately correlated with eGFR (r=0.445, P<0.001). Multivariate regression identified the urine albumincreatinine ratio (ACR) (adjusted odds ratio [aOR], 1.122; 95% confidence interval [CI], -0.007 to, 0.000; P=0.030) and VIF2 (aOR, 1.114; 95% CI, 0.466 to 1.235; P<0.001) were independently associated with eGFR.
Conclusion
The VI measured by drawing a region of interest along the border of the transplanted kidney in SMI (VIF2) is highly reproducible and correlates well with eGFR. Both VIF2 and ACR independently predict eGFR.
5.Endoscopic Surgery for Deeply Located Intracranial Cysts: Risk Factors for Re-Operation and Symptom Improvement
Jun Kyu HWANG ; Ju-Seong KIM ; Eun Kyung PARK ; Kyu Won SHIM ; Dong-Seok KIM
Yonsei Medical Journal 2025;66(2):87-93
Purpose:
We investigated the results of endoscopic fenestration for deeply located intracranial cysts (DLICs), risk factors for reoperation, and symptom improvement.
Materials and Methods:
We included 51 patients with DLICs who underwent endoscopic fenestration between November 2006 and October 2022. The median age was 5±20 years (6 days–67 years), and 36 (70.6%) patients were aged <20 years. The male-tofemale ratio was 1.3:1. The ventriculoscope was used to fenestrate the cysts, which had diameters under 4.5 mm. The volume of DLICs was measured separately on serial magnetic resonance imaging, and the patients were followed up for 32±40 months.
Results:
The mean preoperative volume of DLICs was 63.5±87.4 cm, 3 , which decreased to 23.7±56.2 cm 3postoperatively, with a 45.4%±32.1% decrease rate in 32 months. All DLICs were approached appropriately, avoiding the eloquent areas. Overall, 39 (76.5%) patients showed symptom improvement after a single operation, which was preserved without recurrence, whereas 12 (23.5%) underwent a second operation [shunting (17.6%) or repeating the endoscopic fenestration (5.9%)] owing to symptom aggravation and recurrent cysts. Patients aged <12 months showed 7.4 times more re-operation rate (p>0.046) and 7.4 times less symptom improvement (p=0.038) compared to those with older age. Females showed 6.5 times more re-operation rate (p=0.037) and 7.1 times less symptom improvement (p=0.027) than males. No patients experienced complications such as cerebrospinal fluid leakage, postoperative hemorrhage, or infection.
Conclusion
Endoscopic surgery is feasible for the treatment of DLICs. Female sex and age <12 months are risk factors for re-operation and less symptom improvement.
6.Predisposing Risk Factors Affecting Reversibility of Left Ventricular Diastolic Filling Pattern in Patients with Preserved Ejection Fraction
Dong-Gil KIM ; Sungsoo CHO ; Seongjin PARK ; Gi Rim KIM ; Kyu-Yong KO ; Sung Eun KIM ; Ji-won HWANG ; Joon-Hyung DOH ; Sung Uk KWON ; Jae-Jin KWAK ; June NAMGUNG ; Sung Woo CHO
Yonsei Medical Journal 2025;66(1):1-8
Purpose:
Improvement of left ventricular (LV) diastolic dysfunction (DD) is known to be a good prognostic factor in patients with heart failure with reduced ejection fraction (EF). In the present study, we investigated the predisposing risk factors affecting the reversibility of LV diastolic filling pattern (DFP) in patients with preserved EF.
Materials and Methods:
A total of 600 patients with pseudonormal LVDFP and preserved EF who underwent follow-up echocardiography were enrolled between 2011 and 2020. We compared their index and follow-up echocardiography findings and determined the predisposing risk factor affecting the reversibility of LVDFP.
Results:
Comparing the index and follow-up echocardiography findings showed that 379 (63%) patients had improved to normal or impaired relaxation LVDFP (improved group) and 221 (37%) patients had maintained or worsened LVDFP (unimproved group).The incidence of paroxysmal atrial fibrillation (PAF) was significantly higher in the unimproved group than in the improved group (4.7% vs. 9.5%, p=0.026). After adjustment for relevant clinical risk factors of diastolic dysfunction, PAF was determined to be an independent predisposing risk factor for the unimproved LVDFP (odds ratio: 2.10, 95% confidence interval: 1.06–4.15, p=0.033).Among the parameters of diastolic dysfunction in follow-up echocardiography, the left atrial volume index, mean E/A ratio, and E/e' were significantly improved in patients without PAF but remained in patients with PAF.
Conclusion
We identified that PAF was an independent predisposing risk factor of the unimproved LVDFP in patients with pseudonormal LVDFP and preserved EF. Therefore, early detection and management of PAF might be required in patients with LVDD and preserved EF to prevent adverse cardiovascular events.
7.Association of COX-2 Selectivity in Pain Medication Use with Endometriosis Incidence:Retrospective Cohort Study
Jongchan PARK ; Hye Jin CHANG ; Kyung Joo HWANG ; Sun Hyung YUM ; Chang Eun PARK ; Joo Hee KIM ; Miran KIM
Yonsei Medical Journal 2025;66(6):374-382
Purpose:
This retrospective cohort study aimed to investigate the association between the use of pain medications with varying cyclooxygenase-2 (COX-2) selectivity and the incidence of endometriosis (EMS) in women.
Materials and Methods:
Medical records from January 1, 1994, to December 31, 2022, were retrospectively analyzed. The cohort included 33406 patients diagnosed with any pain-related condition who were prescribed either selective COX-2 inhibitors or nonsteroidal anti-inflammatory drugs (NSAIDs). Patients were followed for up to 5 years from the cohort entry date. The incidence of EMS was compared between the two medication groups using Cox proportional hazards models, adjusting for confounding factors such as age, past drug use, and prior diagnosis.
Results:
The incidence rates of EMS were 3.00 per 1000 person-years in the COX-2 inhibitor group and 3.97 per 1000 person-years in the NSAIDs group. After adjustment for confounders, the hazard ratio for EMS incidence in the COX-2 inhibitor group compared to the NSAIDs group was 0.77 [95% confidence interval (CI), 0.63 to 0.93; p<0.01], indicating a significantly lower risk in the COX-2 inhibitor group. Subgroup analysis revealed that this association was particularly significant in younger women aged 20– 44 years, with a hazard ratio of 0.71 (95% CI, 0.54 to 0.95; p<0.05) in this age group.
Conclusion
The findings suggest that COX-2 inhibitors may reduce the incidence of EMS compared to traditional NSAIDs, highlighting their potential as a strategic option for managing EMS, particularly among younger women. Further prospective studies are needed to confirm these findings.
8.Biennial Mammography Performance in the Korean National Cancer Screening Program From 2009 to 2020
Dong Jun KIM ; Nan-He YOON ; Jae Kwan JUN ; Mina SUH ; Sunhwa LEE ; Seongju KIM ; Horim A. HWANG ; Seung Eun JUNG ; Hooyeon LEE
Korean Journal of Radiology 2025;26(4):313-323
Objective:
Mammography is essential for reducing breast cancer mortality; however, its performance varies globally. This study aimed to evaluate mammography screening outcomes in Korea over 12 years and investigate regional variations.
Materials and Methods:
We analyzed mammography data from 42 million Korean women, aged 40 years and older, who participated in the Korean National Cancer Screening Program (KNCSP) from 2009 to 2020. Performance metrics—including recall rate (RR), positive predictive value (PPV), sensitivity, specificity, false positive rate (FPR), cancer detection rate (CDR), interval cancer rate (ICR), and dense breast rate (DBR), were computed. Twelve-year trends in these metrics were analyzed using Joinpoint regression. Regional variations were also examined across Korea’s 237 districts, stratified by age groups.
Results:
From 2009 to 2020, 42165405 mammography screenings were conducted through the KNCSP, increasing from 2821132 screenings in 2009 to 3596204 in 2020. The RR decreased from 17.2% in 2009 to 11.2% in 2020 (average annual percent change [AAPC] = -3.7%), while the PPV increased from 0.8% to 2.8%; AAPC = 10.7%), the CDR increased from 1.5 to 3.1 per 1000; AAPC = 7.3%), and the ICR rose from 0.9 to 1.6 per 1000; (AAPC = 5.2%). Regional variations were noted; however, differences in the RR, sensitivity, specificity, and FPR decreased over time.
Conclusion
While mammography performance improved from 2009 to 2020, the PPV and sensitivity remain suboptimal, underscoring the need for continuous monitoring. Regional disparities in performance, although reduced, persist. These findings provide essential baseline data for improving mammography quality and addressing inequities in breast cancer screening.
9.Establishment of Local Diagnostic Reference Levels for Pediatric Neck CT at Nine University Hospitals in South Korea
Jisun HWANG ; Hee Mang YOON ; Jae-Yeon HWANG ; Young Hun CHOI ; Yun Young LEE ; So Mi LEE ; Young Jin RYU ; Sun Kyoung YOU ; Ji Eun PARK ; Seok Kee LEE
Korean Journal of Radiology 2025;26(1):65-74
Objective:
To establish local diagnostic reference levels (DRLs) for pediatric neck CT based on age, weight, and water-equivalent diameter (WED) across multiple university hospitals in South Korea.
Materials and Methods:
This retrospective study analyzed pediatric neck CT examinations from nine university hospitals, involving patients aged 0–18 years. Data were categorized by age, weight, and WED, and radiation dose metrics, including volume CT dose index (CTDIvol) and dose length product, were recorded. Data retrieval and analysis were conducted using a commercially available dose-management system (Radimetrics, Bayer Healthcare). Local DRLs were established following the International Commission on Radiological Protection guidelines, using the 75th percentile as the reference value.
Results:
A total of 1159 CT examinations were analyzed, including 169 scans from Institution 1, 132 from Institution 2, 126 from Institution 3, 129 from Institution 4, 128 from Institution 5, 105 from Institution 6, 162 from Institution 7, 127 from Institution 8, and 81 from Institution 9. Radiation dose metrics increased with age, weight, and WED, showing significant variability both within and across institutions. For patients weighing less than 10 kg, the DRL for CTDIvol was 5.2 mGy. In the 10–19 kg group, the DRL was 5.8 mGy; in the 20–39 kg group, 7.6 mGy; in the 40–59 kg group, 11.0 mGy; and for patients weighing 60 kg or more, 16.2 mGy. DRLs for CTDIvol by age groups were as follows: 5.3 mGy for infants under 1 year, 5.7 mGy for children aged 1–4 years, 7.6 mGy for ages 5–9 years, 11.2 mGy for ages 10–14 years, and 15.6 mGy for patients 15 years or older.
Conclusion
Local DRLs for pediatric neck CT were established based on age, weight, and WED across nine university hospitals in South Korea.
10.Ultrafast MRI for Pediatric Brain Assessment in Routine Clinical Practice
Hee Eun MOON ; Ji Young HA ; Jae Won CHOI ; Seung Hyun LEE ; Jae-Yeon HWANG ; Young Hun CHOI ; Jung-Eun CHEON ; Yeon Jin CHO
Korean Journal of Radiology 2025;26(1):75-87
Objective:
To assess the feasibility of ultrafast brain magnetic resonance imaging (MRI) in pediatric patients.
Materials and Methods:
We retrospectively reviewed 194 pediatric patients aged 0 to 19 years (median 10.2 years) who underwent both ultrafast and conventional brain MRI between May 2019 and August 2020. Ultrafast MRI sequences included T1 and T2-weighted images (T1WI and T2WI), fluid-attenuated inversion recovery (FLAIR), T2*-weighted image (T2*WI), and diffusion-weighted image (DWI). Qualitative image quality and lesion evaluations were conducted on 5-point Likert scales by two blinded radiologists, with quantitative assessment of lesion count and size on T1WI, T2WI, and FLAIR sequences for each protocol. Wilcoxon signed-rank tests and intraclass correlation coefficient (ICC) analyses were used for comparison.
Results:
The total scan times for equivalent image contrasts were 1 minute 44 seconds for ultrafast MRI and 15 minutes 30 seconds for conventional MRI. Overall, image quality was lower in ultrafast MRI than in conventional MRI, with mean quality scores ranging from 2.0 to 4.8 for ultrafast MRI and 4.8 to 5.0 for conventional MRI across sequences (P < 0.001 for T1WI, T2WI, FLAIR, and T2*WI for both readers; P = 0.018 [reader 1] and 0.031 [reader 2] for DWI). Lesion detection rates on ultrafast MRI relative to conventional MRI were as follows: T1WI, 97.1%; T2WI, 99.6%; FLAIR, 92.9%; T2*WI, 74.1%; and DWI, 100%. The ICC (95% confidence interval) for lesion size measurements between ultrafast and conventional MRI was as follows: T1WI, 0.998 (0.996–0.999); T2WI, 0.998 (0.997–0.999); and FLAIR, 0.99 (0.985–0.994).
Conclusion
Ultrafast MRI significantly reduces scan time and provides acceptable results, albeit with slightly lower image quality than conventional MRI, for evaluating intracranial abnormalities in pediatric patients.

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