1.Optimization of Natural Killer Cell Expansion with K562-mbIL-18/-21 Feeder Cells and Assurance of Feeder Cell-Free Products
Hantae JO ; Yujung JO ; Seung Kwon KOH ; Mijeong LEE ; Jinho KIM ; SoonHo KWEON ; Jeehun PARK ; Hyun‑Young KIM ; Duck CHO
Annals of Laboratory Medicine 2026;46(2):180-189
Background:
Cancer cell line-derived feeder cells enhance natural killer (NK) cell expansion; however, concerns regarding viable residual feeder cells in the final product limit their use. Evidence supporting the safety of NK-sensitive K562-based feeders, even when irradiated, is scarce. We optimized an NK cell expansion protocol using genetically engineered K562-mbIL-18/-21 (GE-K562) feeder cells and clinical-grade media and confirmed the absence of residual feeder cells.
Methods:
NK cell expansion efficiency was compared between feeder-free and feederbased systems using CTS NK-Xpander Medium. To achieve optimal NK expansion, various peripheral blood mononuclear cell (PBMC)-to-feeder ratios and re-stimulation frequencies were tested over 21 days. Flow cytometry and BCR::ABL1 quantitative reverse transcription PCR (RT-qPCR) were used to confirm the absence of feeder cells in the final NK cell product.
Results:
Feeder-based systems showed superior NK cell fold expansion compared with that of feeder-free systems. Among feeder-based conditions, NK cells expanded 5,224-fold at a 2:1 PBMC-to-feeder ratio after 3 weeks, relative to 1,450-fold at a 6:1 ratio (P < 0.05).Re-stimulation on days 7 and 14 further increased expansion up to 261,457-fold. Irradiated feeder cells showed no proliferation and were eliminated within 3–6 days. On day 21, flow cytometry and BCR::ABL1 RT-qPCR results confirmed the absence of residual feeder cells.
Conclusions
Our optimized NK cell expansion protocol using irradiated GE-K562 feeder cells and clinical-grade media offers a safe and scalable approach to generating large numbers of NK cells, supporting its potential use in clinical immunotherapy applications.
2.Improving prediction of ypT0–1N0 response in rectal cancer: the added value of gross tumor type to magnetic resonance tumor regression grade after chemoradiotherapy in a retrospective cohort study
Kyong-Min KANG ; Mi-Jeong CHOI ; Hong-min AHN ; Heung-Kwon OH ; Duck-Woo KIM ; Jungheum CHO ; Won CHANG ; Young Hoon KIM ; Kyoung Ho LEE ; Yu Kyung JUN ; Yonghoon CHOI ; Sung-Bum KANG
Annals of Surgical Treatment and Research 2026;110(4):237-245
Purpose:
While MRI-based tumor regression grade (mrTRG) has shown promise in evaluating pathologic response to concurrent chemoradiotherapy (CCRT) in rectal cancer, its ability to predict pathologic complete response remains limited.This study aimed to enhance mrTRG’s diagnostic performance in predicting ypT0–1N0 status, a key factor in considering non-radical management after CCRT for locally advanced rectal cancer (LARC).
Methods:
This retrospective study included 430 patients with LARC who underwent radical resection following CCRT at a single referral hospital between April 2018 and September 2024. Multivariable logistic regression was used to identify predictive factors associated with achieving ypT0–1N0 status. The diagnostic performances of mrTRG1–2 alone and in combination with other factors were assessed by comparing sensitivity, specificity, positive-predictive value (PPV), negative-predictive value, and area under the curve (AUC).
Results:
Ninety-three patients (21.6%) achieved ypT0–1N0. In the multivariable analysis, fungating type, cT1–2, and mrTRG1–2 were independent predictors for ypT0–1N0. Integrating mrTRG with gross tumor type yielded the highest AUC of 0.689 among the combined models. For predicting ypT0–1N0, the combination of mrTRG and gross tumor type improved PPV (79.2% vs. 41.5% for mrTRG alone) while also demonstrating enhanced sensitivity compared with ycT0–1N0, the conventional MRI-based predictor (40.9% vs. 22.6%).
Conclusion
This study demonstrated that combining mrTRG and gross tumor type improved the PPV of mrTRG in predicting ypT0–1N0 after CCRT in LARC. Further studies are warranted to validate the role of gross tumor type in refining predictive systems for selecting candidates for non-radical treatment.
3.Urinary mRNA biomarkers for the noninvasive diagnosis of calcineurin inhibitor toxicity in kidney transplant recipients with graft dysfunction: a retrospective study
Jihyun BAEK ; Jung-Woo SEO ; Hyeon Seok HWANG ; So-Young LEE ; Hye Yun JEONG ; Yang Gyun KIM ; Ju-Young MOON ; Jin Sug KIM ; Kyung-Hwan JEONG ; Byung Ha CHUNG ; Chan-Duck KIM ; Jae Berm PARK ; Yu Ho LEE ; Sang-Ho LEE
Clinical Transplantation and Research 2025;39(4):346-354
Background:
Calcineurin inhibitor (CNI) toxicity is a significant cause of graft dysfunction in kidney transplant recipients, yet distinguishing it from acute rejection (AR) and acute tubular necrosis (ATN) remains challenging. This study investigated the use of urinary mRNA biomarkers as a noninvasive tool for identifying CNI toxicity.
Methods:
We retrospectively enrolled 110 kidney transplant recipients and classified them into four groups based on pathological findings: stable graft function (n=35), CNI toxicity (n=25), AR (n=30), and ATN (n=20). Candidate biomarkers were selected using the GEO database. Urinary mRNA was extracted from cell pellets, reverse-transcribed, and quantified by real-time polymerase chain reaction.
Results:
Estimated glomerular filtration rates were comparable among the CNI toxicity, AR, and ATN groups. Four transcripts (LTF, NNMT, WFDC2, and HIF1A) were identified as candidate biomarkers. Urinary mRNA levels of LTF, NNMT, and HIF1A were significantly lower in the CNI toxicity group than the AR group. NNMT and HIF1A levels were also significantly lower than those observed in the ATN group. In contrast, WFDC2 levels did not differ significantly across groups. A three-gene signature (LTF, NNMT, and HIF1A) effectively differentiated CNI toxicity from AR and ATN (area under the curve [AUC], 0.867;95% confidence interval [CI], 0.787–0.947) and significantly enhanced the diagnostic performance of the clinical variable-based model (AUC increased from 0.776; 95% CI, 0.660–0.892, to 0.934; 95% CI, 0.881–0.986).
Conclusions
Urinary mRNA levels of LTF, NNMT, and HIF1A may serve as useful biomarkers for identifying CNI toxicity in kidney transplant recipients with graft dysfunction.
4.Effect of immunosuppressive agents on clinical outcomes in idiopathic membranous nephropathy
Ji-Young CHOI ; Ho Jun CHIN ; Hajeong LEE ; Yena JEON ; Jeong-Hoon LIM ; Hee-Yeon JUNG ; Jang-Hee CHO ; Chan-Duck KIM ; Yong-Lim KIM ; Sun-Hee PARK
Kidney Research and Clinical Practice 2024;43(5):635-647
Few comparative studies on the effects of immunosuppressants in patients with idiopathic membranous nephropathy have been conducted. Methods: Data from 489 patients who received conservative treatment or immunosuppressants were retrospectively analyzed by propensity score matching. Primary outcomes were complete or partial remission (CR or PR) of proteinuria, and secondary outcomes were renal survival and infection. Results: Of the 489 patients, 357 (73.0%) received immunosuppressants. Propensity score matching identified 82 patients from the conservative group and 82 patients in the immunosuppressant group. CR or PR at 12 months was significantly higher in the immunosuppressant group compared with the conservative group for the total population (p = 0.002) and the propensity score-matched population (p = 0.02). The use of immunosuppressants was significantly more effective with respect to achieving a CR or PR at 12 months in patients who were aged <65 years or female, or who had a proteinuria level of ≥4.0 g/g or an estimated glomerular filtration rate of ≥60 mL/min/1.73 m2 (p < 0.05). Renal survival was similar between patients receiving immunosuppressants and conservative treatment in both the total and matched populations. The immunosuppressant group (21.8%) had a significantly higher incidence of infections compared with the conservative group (13.6%) for the total population (p = 0.03), but statistical significance disappeared in the matched population (p > 0.99). Conclusion: The remission rate was significantly higher in the immunosuppressant group than in the conservative group, particularly in the subgroup of patients who were young or female, or those with heavy proteinuria loads or good renal function.
5.Effect of immunosuppressive agents on clinical outcomes in idiopathic membranous nephropathy
Ji-Young CHOI ; Ho Jun CHIN ; Hajeong LEE ; Yena JEON ; Jeong-Hoon LIM ; Hee-Yeon JUNG ; Jang-Hee CHO ; Chan-Duck KIM ; Yong-Lim KIM ; Sun-Hee PARK
Kidney Research and Clinical Practice 2024;43(5):635-647
Few comparative studies on the effects of immunosuppressants in patients with idiopathic membranous nephropathy have been conducted. Methods: Data from 489 patients who received conservative treatment or immunosuppressants were retrospectively analyzed by propensity score matching. Primary outcomes were complete or partial remission (CR or PR) of proteinuria, and secondary outcomes were renal survival and infection. Results: Of the 489 patients, 357 (73.0%) received immunosuppressants. Propensity score matching identified 82 patients from the conservative group and 82 patients in the immunosuppressant group. CR or PR at 12 months was significantly higher in the immunosuppressant group compared with the conservative group for the total population (p = 0.002) and the propensity score-matched population (p = 0.02). The use of immunosuppressants was significantly more effective with respect to achieving a CR or PR at 12 months in patients who were aged <65 years or female, or who had a proteinuria level of ≥4.0 g/g or an estimated glomerular filtration rate of ≥60 mL/min/1.73 m2 (p < 0.05). Renal survival was similar between patients receiving immunosuppressants and conservative treatment in both the total and matched populations. The immunosuppressant group (21.8%) had a significantly higher incidence of infections compared with the conservative group (13.6%) for the total population (p = 0.03), but statistical significance disappeared in the matched population (p > 0.99). Conclusion: The remission rate was significantly higher in the immunosuppressant group than in the conservative group, particularly in the subgroup of patients who were young or female, or those with heavy proteinuria loads or good renal function.
6.Effect of immunosuppressive agents on clinical outcomes in idiopathic membranous nephropathy
Ji-Young CHOI ; Ho Jun CHIN ; Hajeong LEE ; Yena JEON ; Jeong-Hoon LIM ; Hee-Yeon JUNG ; Jang-Hee CHO ; Chan-Duck KIM ; Yong-Lim KIM ; Sun-Hee PARK
Kidney Research and Clinical Practice 2024;43(5):635-647
Few comparative studies on the effects of immunosuppressants in patients with idiopathic membranous nephropathy have been conducted. Methods: Data from 489 patients who received conservative treatment or immunosuppressants were retrospectively analyzed by propensity score matching. Primary outcomes were complete or partial remission (CR or PR) of proteinuria, and secondary outcomes were renal survival and infection. Results: Of the 489 patients, 357 (73.0%) received immunosuppressants. Propensity score matching identified 82 patients from the conservative group and 82 patients in the immunosuppressant group. CR or PR at 12 months was significantly higher in the immunosuppressant group compared with the conservative group for the total population (p = 0.002) and the propensity score-matched population (p = 0.02). The use of immunosuppressants was significantly more effective with respect to achieving a CR or PR at 12 months in patients who were aged <65 years or female, or who had a proteinuria level of ≥4.0 g/g or an estimated glomerular filtration rate of ≥60 mL/min/1.73 m2 (p < 0.05). Renal survival was similar between patients receiving immunosuppressants and conservative treatment in both the total and matched populations. The immunosuppressant group (21.8%) had a significantly higher incidence of infections compared with the conservative group (13.6%) for the total population (p = 0.03), but statistical significance disappeared in the matched population (p > 0.99). Conclusion: The remission rate was significantly higher in the immunosuppressant group than in the conservative group, particularly in the subgroup of patients who were young or female, or those with heavy proteinuria loads or good renal function.
7.The mortality of patients with sepsis increases in the first month of a new academic year
Sukyo LEE ; Sungjin KIM ; Sejoong AHN ; Hanjin CHO ; Sungwoo MOON ; Young Duck CHO ; Jong-Hak PARK
Clinical and Experimental Emergency Medicine 2024;11(2):161-170
Objective:
Many studies have examined the July effect. However, little is known about the July effect in sepsis. We hypothesized that the July effect would result in worse outcomes for patients with sepsis.
Methods:
Data from patients with sepsis, collected prospectively between January 2018 and December 2021, were analyzed. In Korea, the new academic year starts on March 1, so the “July effect” appears in March. The primary outcome was 30-day mortality. Secondary outcomes included adherence to the Surviving Sepsis Campaign bundle. Outcomes in March were compared to other months. A multivariate Cox proportional hazard regression was performed to adjust for confounders.
Results:
We included 843 patients. There were no significant differences in sepsis severity. The 30-day mortality in March was higher (49.0% vs. 28.5%, P<0.001). However, there was no difference in bundle adherence in March (42.2% vs. 48.0%, P=0.264). The multivariate Cox proportional hazard regression showed that the July effect was associated with 30-day mortality in patients with sepsis (adjusted hazard ratio, 1.925; 95% confidence interval, 1.405–2.638; P<0.001).
Conclusion
The July effect was associated with 30-day mortality in patients with sepsis. However, bundle adherence did not differ. These results suggest that the increase in mortality during the turnover period might be related to unmeasured in-hospital management. Intensive supervision and education of residents caring for patients with sepsis is needed in the beginning of training.
8.Long-Term Longitudinal Choroidal Thickness Changes after Intravitreal Anti-Vascular Endothelial Growth Factor Injections in Patients with Neovascular Age-Related Macular Degeneration
Daniel Duck-Jin HWANG ; A Young LEE
Journal of Retina 2024;9(2):162-168
Purpose:
To investigate the long-term effects of intravitreal anti-vascular endothelial growth factor injection on choroidal thickness and its correlation with visual acuity (VA) in neovascular age-related macular degeneration (nAMD).
Methods:
This retrospective study evaluated VA, central macular thickness (CMT), and subfoveal choroidal thickness (SFCT) using spectral domain optical coherence tomography at baseline, followed by assessments for up to five years post-injection. Comparisons were made between nAMD and fellow eyes, as well as between baseline and post-injection values within each group. A multiple regression model was used to analyze factors influencing final VA, including baseline VA, age, sex, number of injections, nAMD subtype, baseline CMT and SFCT, and final CMT and SFCT.
Results:
A total of 57 patients was included in this study. VA improved significantly in nAMD eyes up to one year after injection and then declined. Compared to fellow eyes, nAMD eyes had significantly poorer VA over the entire follow-up. In nAMD eyes, SFCT decreased significantly at each annual follow-up visit (p < 0.001 at every visit). The SFCT of nAMD and fellow eyes showed no significant difference at baseline and after one year. However, a significant difference was observed from the second year onward. Final VA significantly correlated only with baseline VA (standardized coefficients Beta = 0.380, p = 0.011).
Conclusions
The SFCT of nAMD eyes significantly decreased each year, becoming thinner than fellow eyes from the second year on.Throughout follow-up, nAMD eyes had poorer VA than fellow eyes and final VA of nAMD eyes correlated only with baseline VA.
9.Effect of immunosuppressive agents on clinical outcomes in idiopathic membranous nephropathy
Ji-Young CHOI ; Ho Jun CHIN ; Hajeong LEE ; Yena JEON ; Jeong-Hoon LIM ; Hee-Yeon JUNG ; Jang-Hee CHO ; Chan-Duck KIM ; Yong-Lim KIM ; Sun-Hee PARK
Kidney Research and Clinical Practice 2024;43(5):635-647
Few comparative studies on the effects of immunosuppressants in patients with idiopathic membranous nephropathy have been conducted. Methods: Data from 489 patients who received conservative treatment or immunosuppressants were retrospectively analyzed by propensity score matching. Primary outcomes were complete or partial remission (CR or PR) of proteinuria, and secondary outcomes were renal survival and infection. Results: Of the 489 patients, 357 (73.0%) received immunosuppressants. Propensity score matching identified 82 patients from the conservative group and 82 patients in the immunosuppressant group. CR or PR at 12 months was significantly higher in the immunosuppressant group compared with the conservative group for the total population (p = 0.002) and the propensity score-matched population (p = 0.02). The use of immunosuppressants was significantly more effective with respect to achieving a CR or PR at 12 months in patients who were aged <65 years or female, or who had a proteinuria level of ≥4.0 g/g or an estimated glomerular filtration rate of ≥60 mL/min/1.73 m2 (p < 0.05). Renal survival was similar between patients receiving immunosuppressants and conservative treatment in both the total and matched populations. The immunosuppressant group (21.8%) had a significantly higher incidence of infections compared with the conservative group (13.6%) for the total population (p = 0.03), but statistical significance disappeared in the matched population (p > 0.99). Conclusion: The remission rate was significantly higher in the immunosuppressant group than in the conservative group, particularly in the subgroup of patients who were young or female, or those with heavy proteinuria loads or good renal function.
10.Clinical Indications for RHD Genotyping in Koreans
Jong Hyeon LEE ; Jiyoung SEO ; Min-Young PARK ; Jong Kwon LEE ; Duck CHO
Korean Journal of Blood Transfusion 2024;35(1):27-32
RHD genotyping is used primarily when serological tests alone are insufficient to accurately determine the RhD blood type, especially in RhD-negative or RhD variant (D variant) cases. The frequency of RhD-negative and D variants varies significantly according to ethnicity, influencing clinical utilization differently in Korea and Europe.RHD genotyping has multiple applications, including non-invasive prenatal testing, assessment of RhIG administration suitability, identification of weak D and Asian-type DEL in patients, confirmation of D variants in donors, and determination of RhD blood type in patients with weak or discrepant D antigen results. Specifically, detecting Asian-type DEL in serologically RhD-negative individuals is crucial for Koreans, while accurately identifying Weak D types 1, 2, 3, 4.0, and 4.1 in serologically RhD weak-positive samples is vital for Europeans.

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