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.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.
5.A Case of Extracranial Anaplastic Meningioma Presenting as a Solitary Scalp Nodule
Seung Soo LEE ; Jeong-Hyun HWANG ; Ho Yun CHUNG ; Man-Hoon HAN ; Mee-Seon KIM ; Jun Young KIM ; Kyung Duck PARK ; Yong Hyun JANG ; Weon Ju LEE ; Seok-Jong LEE ; Dae-Lyong HA
Korean Journal of Dermatology 2024;62(7):407-411
Meningiomas are common intracranial tumors; however, reports on extracranial cutaneous meningiomas are exceedingly rare. A 77-year-old woman visited our hospital with an asymptomatic child fist-sized mass on the scalp.Biopsy results indicated nuclear atypia and mitoses of sarcomatous cells. Brain magnetic resonance imaging revealed a subgaleal mass with strong enhancement. Suspecting sarcoma, wide excision was performed jointly by the departments of plastic surgery and neurosurgery, during which no evidence of cranial invasion was noted. In the surgical specimen, numerous mitoses of sarcomatous cells and poorly formed nests of epithelioid cells were observed. This led to the diagnosis of anaplastic meningioma without intracranial origin. Subsequently, the patient received adjuvant radiotherapy and is currently under close follow-up. Anaplastic meningioma is rare, but early diagnosis is important as it enables timely and appropriate treatment, thus, improving survival rates. Dermatologists should remain vigilant as meningiomas can manifest as cutaneous scalp nodules, and their accurate diagnosis can profoundly impact prognosis.
6.Diagnostic Process of Subcorneal Pustular Dermatosis: A Case Report
Gi Ung HA ; Seok-Jong LEE ; Weon Ju LEE ; Yong Hyun JANG ; Jun Young KIM ; Dae-Lyong HA ; Kyung Duck PARK
Korean Journal of Dermatology 2024;62(3):169-171
A 54-year-old man presented to our outpatient clinic with generalized pruritic millet-sized vesicles, pustules, and crusts on the whole body over the past 10 years, which were more dominant in the lower extremities. Due to the difficulty in diagnosis, a series of histopathologic examinations were conducted during the treatment course, and the findings were similar: subcorneal pustules with neutrophils, superficial perivascular and dermal infiltration of lymphocytes, neutrophils, and eosinophils, with no sign of acantholysis. The patient was treated with cyclosporine, prednisolone, doxycycline, colchicine, sulfasalazine, and acitretin; however, his condition did not improve. After showing a dramatic improvement with dapsone, he was finally diagnosed with subcorneal pustular dermatosis (SPD).Various medications commonly used in inflammatory and immunobullous skin diseases were tried but failed to improve the condition; the patient showed a dramatic response only to dapsone. Due to its rarity, careful attention and repeated biopsies are required for diagnosing SPD.
7.Cutaneous Nontuberculous Mycobacterial Infection Misdiagnosed as Rheumatoid Nodule in a Patient with Rheumatoid Arthritis
Nam Gyoung HA ; Dae-Lyong HA ; Jun Young KIM ; Yong Hyung JANG ; Weon Ju LEE ; Seok Jong LEE ; Kyung Duck PARK
Korean Journal of Dermatology 2024;62(4):242-246
Owing to advances in diagnostics and the increase in invasive procedures, and immunocompromised patients, cutaneous nontuberculous mycobacteria (NTM) infection is rising. NTM should be suspected in patients with persistent skin lesions refractory to treatment with a history of immunosuppression or skin injury. A 59-year-old woman presented with a 4-week history of multiple erythematous tender nodules on left arm. A year prior, multiple nodules appeared on left hand dorsum, followed by recurrent suppurative nodules in left arm. She has been taking methotrexate and leflunomide for 7 years due to rheumatoid arthritis (RA). Skin biopsy revealed granulomatous inflammation, and NTM polymerase chain reaction test was positive. Furthermore, she had cut her left finger with a knife 14 months ago. Based on these findings, cutaneous NTM infection was diagnosed. Herein, we report a case of cutaneous NTM infection in an immunosuppressed patient with RA, emphasizing differentiating subcutaneous nodules from rheumatoid nodules in RA.
8.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.
9.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.
10.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.

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