2.A Novel Anti-Fibrotic Role of G-Protein-Coupled Receptor 119 in Hepatic Stellate Cells
Jeongwoo PARK ; Min Hoo LEE ; Hyun Young KIM ; Hyo Seon KIM ; Sang Kyum KIM ; Jin Won YANG ; Keon Wook KANG
Biomolecules & Therapeutics 2026;34(3):666-675
Liver fibrosis arises from chronic hepatic injury and remains a major clinical challenge due to the lack of effective therapies.Although G-protein-coupled receptor 119 (GPR119) has been explored as a metabolic target in type 2 diabetes, its role in liver fibrogenesis is not well understood. In this study, the protein and mRNA expression of GPR119 were detected in mouse primary hepatic stellate cells (HSCs) using immunostaining and reverse transcriptase-polymerase chain reaction. The anti-fibrotic activities of GPR119 agonists were assessed in primary HSCs, LX-2 cells, and a carbon tetrachloride (CCl₄)–induced mouse model of liver fibrosis. Treatment with the GPR119 agonists MBX-2982 and GSK1292263 inhibited HSC activation, suppressed transforming growth factor-β1 (TGFβ1)–induced Smad2/3 phosphorylation, and reduced the expression of fibrogenic genes. In vivo, oral administration of MBX-2982 attenuated collagen accumulation and decreased hepatic α-smooth muscle actin and TGFβ expression in CCl₄-treated mice. Mechanistically, MBX-2982 activated AMP-activated protein kinase (AMPK), and pharmacological inhibition of AMPK reversed its anti-fibrogenic effects. MBX-2982 further reduced Smad3 acetylation by disrupting the interaction between Smad3 and p300 and promoting AMPK-dependent proteasomal degradation of p300. These results identify GPR119 as a regulator of HSC activation and highlight GPR119 agonists as promising therapeutic candidates for liver fibrosis.
3.Safety and Effectiveness of Eribulin in Patients with Advanced or Metastatic Breast Cancer Previously Treated with Anthracyclines and Taxanes in Real-World Clinical Practice: A 6-Year Post-marketing Surveillance Study in South Korea
Yee Soo CHAE ; Kyung A KWON ; Moon Hee LEE ; Mi Sun AHN ; Kyung-Hun LEE ; Su-Jin KOH ; Joohyuk SOHN ; Keon Uk PARK ; Min Young KIM ; Youngji PYO ; Bo Young KIM ; Kyung Hae JUNG
Cancer Research and Treatment 2026;58(2):513-524
Purpose:
This 6-year post-marketing surveillance (PMS) study was conducted in South Korea to evaluate the real-world safety and effectiveness of eribulin in patients with advanced or metastatic breast cancer previously treated with anthracyclines and taxanes.
Materials and Methods:
During the study period (17 August 2012 to 16 August 2018), case-report files (CRFs) of patients receiving eribulin were collected. The main study endpoint was to assess the safety of eribulin. Evaluation of the effectiveness of eribulin was an exploratory endpoint. Patients were followed for 1 year after eribulin initiation.
Results:
CRFs were collected from 64 investigators at 64 sites for 1,079 patients. The safety analysis set (SAS) included 1,001 eribulin recipients; effectiveness was assessed in 244 patients. In the SAS, patients were predominantly female (99.6%), with a median age of 53.0 years, and diagnosed with metastatic breast cancer (92.0%). Eribulin was administered as a median 4th line chemotherapy. A total of 2,124 treatment-emergent adverse events (TEAEs) were reported in 661 patients (66.0%). Neutropenia was the most common TEAE (32.5% of patients), occurring at a median of 9-11 days from initial eribulin administration. Overall response and disease control rates were 31.7% and 95.6%, respectively, and the median duration of eribulin use (time to treatment failure) was 3.0 months.
Conclusion
This large real-world PMS analysis in patients with advanced or metastatic breast cancer demonstrated the effectiveness of eribulin and found no new safety concerns relative to safety information from prior clinical and real-world studies, and approvals in South Korea and other countries.
4.Allogeneic Hematopoietic Stem Cell Transplantation in Pediatric and Young Adult Patients with Chronic Myeloid Leukemia in Tyrosine Kinase Inhibitor Era: A Study of the Korean Blood and Marrow Transplantation Registry
Hee Young JU ; Hyoung Soo CHOI ; Hyeon Jin PARK ; Keon Hee YOO ; Chuhl Joo LYU ; Ho Joon IM ; Min Kyoung KIM ; Yeung-Chul MUN ; Joon Ho MOON ; Sung-Soo YOON ; Eunyoung LEE ; Jae Hoon LEE ; Je-Hwan LEE ; So Young CHONG ; June-Won CHEONG ; Seunghyun WON ;
Cancer Research and Treatment 2026;58(2):632-641
Purpose:
Chronic myeloid leukemia (CML) in children, adolescents, and young adults is rare and differs from older adults. This study evaluated the outcomes of allogeneic hematopoietic stem cell transplantation (HSCT) in young Korean CML patients during the tyrosine kinase inhibitor (TKI) era.
Materials and Methods:
A retrospective analysis of 35 CML patients aged < 40 years who underwent allogeneic HSCT from 2009 to 2019 was conducted using Korean Blood and Marrow Transplantation Registry data. Patients were grouped by age < 20 years at HSCT (group 1, n=15) and 20-40 years at HSCT (group 2, n=20). Survival outcomes including overall survival (OS), relapse-free survival (RFS), and event-free survival (EFS) were analyzed using the Kaplan-Meier method.
Results:
The median time between diagnosis and HSCT was 8.9 months. All the patients achieved engraftment but platelet recovery was significantly slower in group 1 (p=0.034). Acute and chronic graft-versus-host disease occurred in 54.3% and 34.3%, respectively. Five-year OS, RFS, and EFS rates of total patients were 66.8%, 50.8%, and 47.6%, with better OS was observed in group 1 by multivariable analysis (p=0.048). Disease status at HSCT was a significant predictor of OS (p=0.028), RFS (p=0.003), and EFS (p=0.004). Disease progression occurred in 13 out of 35 patients (37.1%); treatment-related mortality accounted for 63.6% of deaths (7 out of 11).
Conclusion
When performed at a younger age, allogeneic HSCT result in superior outcome in CML. Achieving remission before HSCT is critical for improved outcomes, highlighting the importance of pretransplant remission via optimal TKI strategies and minimal residual disease monitoring.
5.Clinical Application of Pharmacogenomics in Stroke Management: Current Evidence and Future Directions
Keon-Joo LEE ; Minkyung KANG ; Eung Joon LEE ; Jaeseong OH ; Na-Young HAN ; Jeong-Yoon LEE ; Joo-Yeon LEE ; Soo Ji LEE ; Stéphanie DEBETTE ; Guillaume PARÉ ; Daniel WOO ; Andrew ELDEIRY ; Young Seo KIM ; Jinkwon KIM ; Jong-Moo PARK ; Juneyoung LEE ; Joohon SUNG ; Jay Chol CHOI ; Hee-Joon BAE
Journal of Stroke 2026;28(1):58-75
Pharmacogenomic variations may significantly influence responses to commonly prescribed stroke medications. Despite accumulating evidence, genetic testing has not yet been widely integrated into stroke care. This review summarizes current evidence and provides practical guidance for clinical implementation. Pharmacogenomic studies and clinical guidelines related to antiplatelet agents, anticoagulants, and statins were reviewed, with particular emphasis on East Asian populations. Substantial evidence supports genotype-guided use of clopidogrel (CYP2C19), warfarin (CYP2C9, VKORC1, CYP4F2), and statins (SLCO1B1, ABCG2). For aspirin, PTGS1/2 and PEAR1 variants have been investigated; however, current data remain insufficient for clinical application. Regarding direct oral anticoagulants (DOACs), candidate genes such as ABCB1 and CES1 demonstrate pharmacokinetic associations, though robust clinical outcome data are lacking. Distinct allele frequencies in East Asians—such as higher prevalence of CYP2C19 and ABCG2 variants—underscore the need for population-specific strategies. Beyond single-gene approaches, polygenic risk scores, pharmacogenomic panels, and integration with multi-omics data and artificial intelligence represent promising directions for personalized therapy. Pharmacogenomic testing can enhance stroke pharmacotherapy, particularly in populations with high frequencies of actionable variants. Broader implementation requires rapid testing platforms, clinician education, tailored clinical guidelines, and real-world validation of aspirin, DOACs, and multi-gene approaches. Future research should expand population-specific studies and integrate pharmacogenomics within the broader framework of precision medicine to ensure equitable clinical benefit.
6.Korean colorectal cancer screening guidelines for asymptomatic, average-risk adults: the 2025 revision
EunKyo KANG ; Jae Myung CHA ; Seo Young KANG ; Kiheon LEE ; Su Young KIM ; Younghoon KIM ; An Na SEO ; Hyo-Jin KANG ; Jong Keon JANG ; Kwang-Pil KO ; Aesun SHIN ; Dae Kyung SOHN ; Youngki HONG ; Eun-Jung CHO ; Minje HAN ; Soo Young KIM ; Hyeon Ji LEE ; Chang Kyun CHOI ; Mina SUH
Journal of the Korean Medical Association 2026;69(3):268-280
Purpose:
To develop the 2025 update to the Korean colorectal cancer (CRC) screening guidelines by systematically evaluating recent evidence, integrating domestic data, and addressing changes since the 2015 guideline revision, thereby providing an evidence-based standard for clinicians and policymakers.
Methods:
A multidisciplinary committee developed the guidelines using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. The process included formulation of three key questions addressing screening efficacy, diagnostic accuracy, and optimal screening age and interval. A systematic review of international guidelines and primary literature was conducted, yielding 327 eligible studies. In addition, a utility-based analysis using a Markov model was performed to determine optimal screening ages and intervals.
Results:
The evidence synthesis identified high-certainty evidence supporting the use of the fecal immunochemical test (FIT) for reducing CRC mortality and moderate-certainty evidence for colonoscopy. Evidence for computed tomographic colonography (CTC) and stool DNA testing was rated as very low certainty. Based on the evidence review and cost-utility analysis, the committee conditionally recommends CRC screening for asymptomatic, average-risk adults aged 45–74 years using either colonoscopy every 10 years or FIT every 1–2 years. CTC and stool DNA testing were not recommended owing to insufficient evidence.
Conclusion
The 2025 Korean Guidelines for Colorectal Cancer Screening present updated, evidence-based recommendations tailored to the domestic healthcare context. By conditionally endorsing both colonoscopy and FIT for individuals aged 45–74 years, these guidelines aim to improve population-level screening effectiveness and reduce the burden of CRC in South Korea.
7.Second Allogeneic Hematopoietic Cell Transplantation Following Graft Failure in Children
Eun Sang YI ; Hee Young JU ; Ji Won LEE ; Ki Woong SUNG ; Jin HUR ; Keon Hee YOO
Journal of Korean Medical Science 2025;40(10):e48-
Background:
Graft failure (GF) is a major complication of allogeneic hematopoietic cell transplantation (allo-HCT). Secondary transplantation has been recognized as a potential curative intervention.
Methods:
This study aimed to investigate the characteristics and outcomes of salvage transplantation by analyzing the patients who underwent a second HCT for GF following the initial allo-HCT between 1998 and 2020.
Results:
Overall, 23 recipients were identified, including 14 and 9 individuals with primary and secondary GF, respectively. Nine recipients underwent a second transplant from the same donor. Familial mismatched donors predominated in the second HCT (86.9%), with reduced-intensity conditioning as the prevailing approach (60.9%). Neutrophil engraftment occurred in 17 patients (73.9%) following the second HCT at a median of 17 days (range: 9–58 days) post-transplantation. However, secondary GF subsequently occurred in 5 patients, and successful engraftment following salvage transplantation was achieved in 12 (52.2%) patients. In the entire study population, the estimated 5-year probability of overall survival (OS) and treatment-related mortality (TRM) were 30.4% and 58.5%, respectively. Among patients who achieved successful engraftment following a second transplantation, the OS and TRM rates were 41.7% and 33.3%, respectively, indicating a trend toward better OS and significantly lower TRM compared to those with GF. Notably, 17 patients died, with infection being the most common cause (n = 12), irrespective of the engraftment status.
Conclusion
A successful engraftment following a second allo-HCT reduced the TRM; however, the OS remained suboptimal. The effective control of infectious diseases remains crucial for patients with GF, regardless of the engraftment status following salvage transplantation.
8.Rapid Recovery From SARS-CoV-2Infection Among Immunocompromised Children Despite Limited Neutralizing Antibody Response: A Virologic and Sero-Immunologic Analysis of a Single-Center Cohort
Doo Ri KIM ; Byoung Kwon PARK ; Jin Yang BAEK ; Areum SHIN ; Ji Won LEE ; Hee Young JU ; Hee Won CHO ; Keon Hee YOO ; Ki Woong SUNG ; Chae-Hong JEONG ; Tae Yeul KIM ; June-Young KOH ; Jae-Hoon KO ; Yae-Jean KIM
Journal of Korean Medical Science 2025;40(12):e52-
Background:
Immunocompromised (IC) pediatric patients are at increased risk of severe acute respiratory syndrome coronavirus 2 infection, but the viral kinetics and seroimmunologic response in pediatric IC patients are not fully understood.
Methods:
From April to June 2022, a prospective cohort study was conducted. IC pediatric patients hospitalized for coronavirus disease 2019 (COVID-19) were enrolled. Serial saliva swab and serum specimens were subjected to reverse transcription polymerase chain reaction assays with mutation sequencing, viral culture, anti-spike-protein, anti-nucleocapsid antibody assays, plaque reduction neutralization test (PRNT) and multiplex cytokine assays.
Results:
Eleven IC children were evaluated. Their COVID-19 symptoms resolved promptly (median, 2.5 days; interquartile range, 2.0–4.3). Saliva swab specimens contained lower viral loads than nasopharyngeal swabs (P = 0.008). All cases were BA.2 infection, and 45.5% tested negative within 14 days by saliva swab from symptom onset. Eight (72.7%) showed a time-dependent increase in BA.2 PRNT titers, followed by rapid waning. Multiplex cytokine assays revealed that monocyte/macrophage activation and Th 1 responses were comparable to those of non-IC adults. Activation of interleukin (IL)-1Ra and IL-6 was brief, and IL-17A was suppressed. Activated interferon (IFN)-γ and IL-18/IL-1F4 signals were observed.
Conclusion
IC pediatric patients rapidly recovered from COVID-19 with low viral loads.Antibody response was limited, but cytokine analysis suggested an enhanced IFN-γ- and IL-18-mediated immune response without excessive activation of inflammatory cascades. To validate our observation, immune cell-based functional studies need to be conducted among IC and non-IC children.
9.Brain Injury and Short-Term Neurodevelopmental Outcomes in Neonates Treated with Respiratory Extracorporeal Membrane Oxygenation: A Single-Center Experience
Keon Hee SEOL ; Byong Sop LEE ; Kyusang YOO ; Joo Hyung ROH ; Jeong Min LEE ; Jung Il KWAK ; Tae-Gyeong KIM ; Juhee PARK ; Ha Na LEE ; Chae Young KIM ; Soo Hyun KIM ; Ji Yoon JEONG ; Euiseok JUNG
Neonatal Medicine 2025;32(1):39-48
Purpose:
This study aimed to characterize the clinical patterns and severity of brain injury in neonates who survived extracorporeal membrane oxygenation (ECMO) therapy for acute respiratory failure during the neonatal period, to evaluate their short-term neurodevelopmental outcomes, and to identify the factors associated with these outcomes.
Methods:
We retrospectively reviewed the medical records of neonates who survived ECMO between 2018 and 2024. Based on brain magnetic resonance imaging (MRI) findings, the patients were classified into two groups: no/mild and moderate/severe brain injury. Neurodevelopmental outcomes were assessed at 12–40 months of age using the Bayley Scale of Infant Development II/III and/or the Korean Developmental Screening Test.
Results:
Among the 19 neonates included in the study, 18 (94.7%) showed varying degrees of brain injury on MRI (mild: 12, moderate: 1, severe: 5). Neonates with moderate/severe brain injury had significantly longer durations of ECMO support and extended durations of mechanical ventilation and were more likely to receive continuous renal replacement therapy than those with no or mild injury. Developmental delay was identified in 36.8% of survivors and was significantly associated with prolonged mechanical ventilation, longer neonatal intensive care unit stays, and a higher incidence of seizures.
Conclusion
Brain injury is frequently observed on MRI in neonates treated with ECMO. However, its direct association with adverse neurodevelopmental outcomes is not definitive. Since MRI findings alone cannot predict developmental outcomes, clinical and environmental factors should be integrated into prognostic assessments.
10.Permanent Congenital Hypothyroidism in Very Low Birth Weight Infants: A Single Center’s Experience
Joo Hyung ROH ; Tae-Gyeong KIM ; Keon Hee SEOL ; Chae Young KIM ; Soo Hyun KIM ; Ji Yoon JEONG ; Ja Hye KIM ; Euiseok JUNG ; Jin-Ho CHOI ; Byong Sop LEE
Neonatal Medicine 2025;32(1):30-38
Purpose:
Congenital hypothyroidism (CH) is a major preventable cause of intellectual disability, particularly in very low birth weight (VLBW) infants, who are at increased risk due to hypothalamic-pituitary-thyroid axis immaturity. Early differentiation between transient CH (TCH) and permanent CH (PCH) is crucial to optimize L-thyroxine (LT4) treatment duration. This study aimed to determine the incidence of PCH among Korean VLBW infants and to identify clinical factors that may aid in distinguishing TCH from PCH.
Methods:
This retrospective cohort study included VLBW infants diagnosed with CH and treated with LT4 at a single tertiary neonatal intensive care unit between 2011 and 2020. Infants requiring LT4 beyond 3 years were classified as PCH, while those who discontinued earlier were considered TCH. Clinical characteristics, neonatal morbidities, and thyroid-related parameters were compared between the groups.
Results:
Among 1,292 VLBW infants, 122 (9.4%) were diagnosed with CH. After excluding deaths and those lost to follow-up, 73 infants were included in the final analysis (TCH, n=50; PCH, n=23). The PCH group had a significantly higher mean gestational age and greater LT4 requirements at both 12 and 36 months of age. Major anomalies were more frequently observed in PCH infants, including congenital heart defects. In multivariate analysis, higher gestational age, the presence of major anomalies, screening thyroid-stimulating hormone (TSH) >10 μIU/mL, and higher LT4 dose at 36 months were significantly associated with PCH.
Conclusion
The incidence of PCH in Korean VLBW infants was relatively higher than that reported in previous studies studies. Screening TSH level and LT4 dose requirements may support individualized follow-up and help distinguish PCH from TCH.

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