1.DNA Damage and Nuclear Anaplasia Induced by Trastuzumab Deruxtecan in Cancer Cells with Variable HER2 Expression and Homologous Recombination Deficiency Status
So Hyeon KIM ; Yoonjung PARK ; Ahrum MIN ; Hye Yeon PARK ; Yu-Jin KIM ; Sujin HAM ; Jiwon KOH ; Seongyeong KIM ; Dae-Won LEE ; Han Suk RYU ; Jin-Soo KIM ; Kyung-Hun LEE ; Seock-Ah IM
Cancer Research and Treatment 2026;58(2):407-422
Purpose:
Human epidermal growth factor receptor 2 (HER2) is amplified or overexpressed in various malignancies, including breast and gastric cancers, and is associated with poor prognosis. Although HER2-targeted therapies, such as trastuzumab, improve outcomes in HER2-positive tumors, resistance often develops, and HER2-low tumors remain largely untargeted. Trastuzumab deruxtecan (T-DXd; DS-8201a) is a HER2-targeted antibody-drug conjugate with potent activity in HER2-positive and HER2-low tumors. This study evaluates its antitumor mechanisms and efficacy in HER2-positive, HER2-low, and homologous recombination deficiency (HRD)–associated models.
Materials and Methods:
Effects of T-DXd were assessed in cancer cell lines with diverse HER2 expression and HRD status. In vivo efficacy was evaluated using a xenograft model derived from HER2-low SNU-601 gastric cancer cells.
Results:
T-DXd reduced HER2 phosphorylation and downstream signaling (AKT, ERK) in HER2-positive cells. It induced DNA damage accumulation, as evidenced by increased γH2AX and p-Chk1 expression, and triggered apoptosis through cleaved poly(ADP-ribose) polymerase and caspase-3 activation, confirmed by annexin V staining. Similar effects were observed in HER2-low cells, with greater sensitivity in HRD cells. In xenografts, T-DXd reduced tumor volume by up to 80% at 4 mg/kg and 10 mg/kg. Histological analyses showed decreased Ki-67 and increased apoptosis. Furthermore, T-DXd induced G2/M cell cycle arrest and nuclear anaplasia, suggesting disruption of chromosomal stability as a potential antitumor mechanism. No significant toxicity, including body weight loss, was observed.
Conclusion
These findings highlight T-DXd’s effectiveness in HER2-low and HRD tumors, supporting its broader clinical application, including strategies targeting DNA damage repair pathways.
2.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.
3.Survival Rates of Patients with Gastric Cancer According to Age and Sex: A Large-Scale Study Using Data from 14,739 Patients
Yonghoon CHOI ; Nayoung KIM ; Ji Hyun KIM ; Hyeong Ho JO ; Hyeon Jeong OH ; Hye Seung LEE ; Yu Kyung JUN ; Hyuk YOON ; Cheol Min SHIN ; Young Soo PARK ; Dong Ho LEE ; So Hyun KANG ; Young Suk PARK ; Sang-Hoon AHN ; Yun-Suhk SUH ; Do Joong PARK ; Hyung Ho KIM ; Ji-Won KIM ; Jin Won KIM ; Keun-Wook LEE ; Won CHANG ; Yoon Jin LEE ; Kyoung Ho LEE ; Young Hoon KIM
Cancer Research and Treatment 2026;58(1):252-263
Purpose:
The male predominance in the incidence of gastric cancer (GC) is established; however, sex differences in the prognosis of GC remain controversial. As such, this study analyzed the prognosis of patients with GC based on age and sex.
Materials and Methods:
Data from 14,739 patients diagnosed with GC at Seoul National University Bundang Hospital between 2003 and 2023 were analyzed. Baseline characteristics, histological types of GC, overall and GC-specific survival rates (age and stage stratification), and associated risk factors were analyzed.
Results:
Females were significantly younger (p < 0.001) and exhibited more gastric body cancers (p < 0.001) and tumors with diffuse-type or poorly differentiated histology (p < 0.001) than males. Females exhibited an advantage over males in terms of overall survival (p=0.004), but not in GC-specific survival. However, age stratification revealed significant sex differences, that females < 50 years of age exhibited survival disadvantages (p < 0.001); however, this trend was reversed with age, and females > 60 years exhibited survival advantages (p < 0.001) for both overall and GC-specific survival. This may be explained by the lower ratio of diffuse-type GC as females age. Furthermore, in the analysis according to stage, females with stage IV disease exhibited significant survival disadvantages, with significantly younger age and a higher proportion of diffuse-type GC which exhibits aggressive features, resulting in poorer survival than in males.
Conclusion
Age and stage stratification revealed significant differences in survival between the sexes, which can be helpful for public health strategies.
4.Effects of Emergency Nurses’ Life-Sustaining Treatment Withdrawal Knowledge, Role Perception, and Job Stress on Providing End-of-Life Care
Hyun Ju PARK ; Eun Ah HONG ; So Hyeon MIN ; Heeje YUN ; Hyung Bok LEE ; Won Ho CHOI
Journal of Hospice and Palliative Care 2025;28(3):89-98
Purpose:
This study aimed to identify predictors of end-of-life (EOL) care provided by emergency nurses in South Korea.
Methods:
A cross-sectional survey was conducted using a structured questionnaire. Data were collected using Google Forms between June 21 and 30, 2022. A total of 154 emergency nurses from 10 tertiary hospitals in a metropolitan area were recruited using convenience sampling, and 139 completed surveys were analyzed. Multiple linear regression was employed to examine the effects of nurses’ knowledge of life-sustaining treatment withdrawal (knowledge), their perceptions of their role in the withdrawal process (role perception), and job stress on EOL care.
Results:
The mean scores for knowledge, role perception, job stress, and EOL care were 13.09±1.75 (max 6), 4.18± 0.44 (max 5), 3.55±0.32 (max 4), and 2.48±0.40 (max 4), respectively. Among the EOL care subdomains, psychological domain scores were the highest. Multiple linear regression analysis indicated that nurses’ role perception significantly predicted EOL care performance, particularly in the psychological (F=3.924, P=0.001) and spiritual (F=2.171, P=0.020) domains.
Conclusion
Despite the challenging environment of the emergency department, nurses who recognize their important role in the process of life-sustaining treatment withdrawal are more likely to provide high-quality EOL care. The perception of nurses’ roles is especially influential on psychological care performance, and alternative approaches may be necessary for spiritual care.
5.Analysis of Characteristics and Risk Factors of Patients with Single Gastric Cancer and Synchronous Multiple Gastric Cancer among 14,603 Patients
Du Hyun SONG ; Nayoung KIM ; Hyeong Ho JO ; Sangbin KIM ; Yonghoon CHOI ; Hyeon Jeong OH ; Hye Seung LEE ; Hyuk YOON ; Cheol Min SHIN ; Young Soo PARK ; Dong Ho LEE ; So Hyun KANG ; Young Suk PARK ; Sang-Hoon AHN ; Yun-Suhk SUH ; Do Joong PARK ; Hyung Ho KIM ; Ji-Won KIM ; Jin Won KIM ; Keun-Wook LEE ; Won CHANG ; Ji Hoon PARK ; Yoon Jin LEE ; Kyoung Ho LEE ; Young Hoon KIM ; Soyeon AHN ; Young-Joon SURH
Gut and Liver 2024;18(2):231-244
Background/Aims:
Synchronous multiple gastric cancer (SMGC) accounts for approximately 6% to 14% of gastric cancer (GC) cases. This study aimed to identify risk factors for SMGC.
Methods:
A total of 14,603 patients diagnosed with GC were prospectively enrolled. Data including age, sex, body mass index, smoking, alcohol consumption, family history, p53 expression, microsatellite instability, cancer classification, lymph node metastasis, and treatment were collected. Risk factors were analyzed using logistic regression analysis between a single GC and SMGC.
Results:
The incidence of SMGC was 4.04%, and that of early GC (EGC) and advanced GC (AGC) was 5.43% and 3.11%, respectively. Patients with SMGC were older (65.33 years vs 61.75 years, p<0.001) and more likely to be male. Lymph node metastasis was found in 27% of patients with SMGC and 32% of patients with single GC. Multivariate analysis showed that SMGC was associated with sex (male odds ratio [OR], 1.669; 95% confidence interval [CI], 1.223 to 2.278; p=0.001), age (≥65 years OR, 1.532; 95% CI, 1.169 to 2.008; p=0.002), and EGC (OR, 1.929; 95% CI, 1.432 to 2.600; p<0.001). Survival rates were affected by Lauren classification, sex, tumor size, cancer type, distant metastasis, and venous invasion but were not related to the number of GCs. However, the survival rate of AGC with SMGC was very high.
Conclusions
SMGC had unique characteristics such as male sex, older age, and EGC, and the survival rate of AGC, in which the intestinal type was much more frequent, was very good (Trial registration number: NCT04973631).
6.Exudative Retinal Detachment after Pembrolizumab Treatment in Metastatic Cutaneous Melanoma
So Hyeon LEE ; Yoon Seok CHOI ; Jin Young KIM ; Yu Min KIM ; Jae Rock DO ; Yong Koo KANG ; Dong Ho PARK ; Jae Pil SHIN
Journal of the Korean Ophthalmological Society 2024;65(6):394-399
Purpose:
To report a case of exudative retinal detachment after using pembrolizumab in a patient with metastatic cutaneous melanoma.Case summary: A 67-year-old woman, diagnosed with malignant melanoma of the right thumb and axillary metastasis, presented with bilateral visual disturbance 3 days after adjuvant chemotherapy with pembrolizumab. Her best corrected visual acuity was 0.2 in the right eye and 0.7 in the left, while the intraocular pressure was 14 mmHg in both eyes. Fundus examination showed serous retinal detachment and choroidal detachment in the right eye, as well as a chorioretinal folding in both eyes. Optical coherence tomography showed exudative retinal detachment and choroidal detachment in the right eye, along with choroidal folding in both eyes. The pembrolizumab was stopped immediately, and the patient began treatment with systemic and topical steroids. After 1 month, the visual acuity improved and there was no exudative retinal detachment or choroidal detachment. However, 3 weeks later, exudative retinal detachment recurred in both eyes. The patient started treatment with oral steroids and cyclosporine, which resulted in the resolution of the exudative retinal detachment after 1 month.
Conclusions
Exudative retinal detachment may occur as a side effect of pembrolizumab treatment. Therefore, a differential diagnosis and appropriate treatment of ocular side effects are necessary.
7.Isolation and Identification of Antifungal Metabolites from Juncus torreyi
Seong Ho PARK ; Ji Won KANG ; Ga Hyeon PARK ; So-Jung JO ; Kyung-Won MIN ; Kyu Song LEE ; Hyun Bong PARK
Natural Product Sciences 2024;30(2):161-166
Plants belonging to the genus Juncus are widely distributed across North America, which are known to make a diverse array of bioactive natural products. In 2022, Juncus torreyi, a species of Juncus, was firstly found in Korea. Morphological and ecological characteristics of the species have been previously investigated;however, bioactive chemical potentials still remain to be explored. In the present work, we focused on the isolation and characterization of metabolites that harbor growth inhibitory activity against a fungal indicator, Candida albicans. Using activity-guided discovery method, we subsequently isolated and purified three metabolites from the most active methylene chloride-soluble fraction. Through NMR and high-resolution ESIOrbitrap-MS data analysis, the metabolites were structurally determined to be juncatrin B (1), ensifolin I (2), and juncusol (3). Metabolites 1–3 were evaluated for their C. albicans growth inhibitory activity and revealed inhibition with an IC 50 value of 74.3, 31.5, and 64.6 μg/mL, respectively.
8.Erratum: Correction of Affiliations in the Article “Establishment of a Nationwide Korean Imaging Cohort of Coronavirus Disease 2019”
Soon Ho YOON ; Soo-Youn HAM ; Bo Da NAM ; Kum Ju CHAE ; Dabee LEE ; Jin Young YOO ; So Hyeon BAK ; Jin Young KIM ; Jin Hwan KIM ; Ki Beom KIM ; Jung Im JUNG ; Jae-Kwang LIM ; Jong Eun LEE ; Myung Jin CHUNG ; Young Kyung LEE ; Young Seon KIM ; Ji Eun JO ; Sang Min LEE ; Woocheol KWON ; Chang Min PARK ; Yun-Hyeon KIM ; Yeon Joo JEONG
Journal of Korean Medical Science 2023;38(34):e298-
9.Loss of Neutralizing Activity of Tixagevimab/Cilgavimab (Evusheld™) Against Omicron BN.1, a Dominant Circulating Strain Following BA.5During the Seventh Domestic Outbreak in Korea in Early 2023
Jinyoung YANG ; Seokhwan HYEON ; Jin Yang BAEK ; Min Seo KANG ; Keon Young LEE ; Young Ho LEE ; Kyungmin HUH ; Sun Young CHO ; Cheol-In KANG ; Doo Ryeon CHUNG ; Kyong Ran PECK ; Gunho WON ; Hye Won LEE ; Kwangwook KIM ; Insu HWANG ; So Yeon LEE ; Byung Chul KIM ; Yoo-kyoung LEE ; Jae-Hoon KO
Journal of Korean Medical Science 2023;38(27):e205-
Tixagevimab/cilgavimab is a monoclonal antibody used to prevent coronavirus disease 2019 among immunocompromised hosts and maintained neutralizing activity against early omicron variants. Omicron BN.1 became a dominant circulating strain in Korea early 2023, but its susceptibility to tixagevimab/cilgavimab is unclear. We conducted plaque reduction neutralization test (PRNT) against BN.1 in a prospective cohort (14 patients and 30 specimens). BN.1 PRNT was conducted for one- and three-months after tixagevimab/ cilgavimab administration and the average PRNT ND 50 of each point was lower than the positive cut-off value of 20 (12.9 ± 4.5 and 13.2 ± 4.2, respectively, P = 0.825). In the paired analyses, tixagevimab/cilgavimab-administered sera could not actively neutralize BN.1 (PRNT ND 50 11.5 ± 2.9, P = 0.001), compared with the reserved activity against BA.5 (ND 50 310.5 ± 180.4). Unlike virus-like particle assay, tixagevimab/cilgavimab was not active against BN.1 in neutralizing assay, and would not be effective in the present predominance of BA.2.75 sublineages.
10.Current Status of Q Fever and the Challenge of Outbreak Preparedness in Korea: One Health Approach to Zoonoses
Yun Sang CHO ; Ji-Hyuk PARK ; Jong Wan KIM ; Jin-Ju LEE ; So Youn YOUN ; Hyeon Seop BYEON ; Hye Won JEONG ; Dong-Min KIM ; Shi Nae YU ; Jang Won YOON ; Dongmi KWAK ; Han Sang YOO ; Ji-Yeon LEE ; Jeong-Ran KWON ; Kyung-Won HWANG ; Jung Yeon HEO
Journal of Korean Medical Science 2023;38(24):e197-
Human Q fever, a zoonosis caused by Coxiella burnetii, presents with diverse clinical manifestations ranging from mild self-limited febrile illnesses to life-threatening complications such as endocarditis or vascular infection. Although acute Q fever is a benign illness with a low mortality rate, a large-scale outbreak of Q fever in the Netherlands led to concerns about the possibility of blood transfusion-related transmission or obstetric complications in pregnant women. Furthermore, a small minority (< 5%) of patients with asymptomatic or symptomatic infection progress to chronic Q fever. Chronic Q fever is fatal in 5–50% of patients if left untreated. In South Korea, Q fever in humans was designated as a notifiable infectious disease in 2006, and the number of Q fever cases has increased sharply since 2015. Nonetheless, it is still considered a neglected and under-recognized infectious disease. In this review, recent trends of human and animal Q fever in South Korea, and public health concerns regarding Q fever outbreaks are reviewed, and we consider how a One Health approach could be applied as a preventive measure to prepare for zoonotic Q fever outbreaks.

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