2.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.
3.Associations of Loneliness With Alcohol Consumption Levels:Based on the 2021 National Mental Health Survey of Korea
Sujin PARK ; Somyung LEE ; Yoonyoung NAM
Journal of Korean Neuropsychiatric Association 2026;65(1):34-43
Objectives:
This study examined the association between loneliness and alcohol consumption among Korean adults and explored the differences across sociodemographic subgroups, including sex, age, income, occupation, and marital status.
Methods:
Data were obtained from the 2021 National Mental Health Survey of Korea, including 5491 adults aged 18 years or older. Loneliness was measured using the Loneliness and Social Isolation Measure-6 (LSIS-6). Alcohol consumption was categorized as abstinence, moderate drinking, or high-risk drinking. Depressive symptoms were classified according to the KoreanComposite International Diagnostic Interview (K-CIDI) criteria. The group differences were assessed using analysis of variance (ANOVA) and chi-square tests. Complex-sample multinomial logistic regression was performed to examine the associations between loneliness and alcohol consumption while adjusting for age, gender, income, occupation, and marital status.
Results:
Sociodemographic characteristics significantly differed across alcohol-use groups. After adjusting for the covariates and depressive symptoms, loneliness remained positively associated with high-risk drinking. Age-stratified analyses suggested that this association was observed only among adults aged 60 years and older. Moderate drinking was not significantly associated with loneliness in all age groups.
Conclusion
Loneliness was independently associated with high-risk drinking in Korean adults, particularly in older adults. These findings highlight the importance of incorporating social isolation and loneliness into alcohol-related screening and prevention strategies, especially for aging populations.
4.Clinical Implications of Circulating Tumor DNA in Multiple Myeloma and Its Precursor Diseases
Sung-Soo PARK ; Na Yung KIM ; Ji-Young LIM ; Jung Yeon LEE ; Sujin YUN ; Yeun-Jun CHUNG ; Seung-Hyun JUNG ; Chang-Ki MIN
Annals of Laboratory Medicine 2025;45(3):279-290
Background:
Genetic alterations play a pivotal role in multiple myeloma (MM) development and therapeutic resistance. Traditionally, the genetic profiling of MM requires invasive bone marrow (BM) procedures; however, these procedures are associated with patient discomfort and cannot fully capture the spatial and temporal heterogeneity of the disease.Therefore, we investigated the clinical implications of liquid biopsy using targeted deep sequencing.
Methods:
We analyzed the genetic profiles of circulating tumor DNA (ctDNA) by targeted deep sequencing from 102 patients, including those with monoclonal gammopathy of undetermined significance (MGUS, N = 7), smoldering MM (N = 6), and symptomatic MM (N = 89).
Results:
The number of ctDNA mutations increased with disease progression from MGUS to MM, with averages of 1.0 mutations in MGUS, 1.8 mutations in smoldering MM, and 1.9 mutations in MM, respectively. Shared mutations between BM and ctDNA were more prevalent in MM (68.9%) than in MGUS (25.0%). RAS/RAF and TP53 mutations were significantly enriched in MM ctDNA. Specific mutations were associated with clinical features in patients with MM: hypercalcemia and TET2 (P = 0.006), renal insufficiency and NRAS (P = 0.012), paramedullary myeloma and TP53(P = 0.02), and extramedullary myeloma and NRAS (P = 0.007). TET2 mutations significantly affected 2-yr progression-free survival (hazard ratio = 7.11, P = 0.003). Serial ctDNA profiling accurately predicted treatment response in patients with MM.
Conclusions
Our findings highlight the potential of liquid biopsy for understanding MM progression and prognosis utilizing a minimally invasive approach, paving the way for its integration into personalized treatment strategies and real-time disease monitoring.
5.Retrohepatic inferior vena cava interposition in living donor liver transplantation for a pediatric patient with advanced hepatoblastoma
Jung-Man NAMGOONG ; Shin HWANG ; Gil-Chun PARK ; Hyunhee KWON ; Suhyeon HA ; Sujin GANG ; Jueun PARK ; Kyung Mo KIM ; Seak Hee OH
Annals of Liver Transplantation 2025;5(1):54-60
Replacement of the retrohepatic inferior vena cava (IVC) after concurrent resection of IVC and tumor-bearing liver is regarded as a feasible living donor liver transplantation (LDLT) technique to cope with tumors around the IVC. This method can make the resection extent of LDLT comparable to that of deceased-donor liver transplantation. We present one pediatric LDLT case with IVC replacement using an enlarged iliac vein conduit to treat advanced hepatoblastoma. The patient was a 33-monthold and 12 kg-weighing girl suffering from large multiple hepatoblastomas invading the retrohepatic IVC. At 2-month waiting after deciding LDLT, we obtained a coldstored iliac vein graft and LDLT was performed with the father’s left lateral section graft. A 1.3 cm-wide and 10 cm-long iliac vein was transformed to be a 2 cm-wide and 5 cm-long vein graft through a double-barrel unification venoplasty. The left lateral section graft was implanted along the standard procedure of LDLT. The patient recovered uneventfully and is undergoing scheduled adjuvant chemotherapy. IVC replacement with vein homograft is a feasible option for LDLT in pediatric patients with advanced liver malignancy.
6.Association between Circadian Rhythm-Disturbing Factors and Metabolic Syndrome in Korean Adults: Korea National Health and Nutrition Examination Survey (2016–2020)
Sujin LEE ; Junhee PARK ; Hyunjin CHO ; Jun Hyun YOO
Korean Journal of Family Medicine 2025;46(3):162-169
Background:
Circadian misalignment is associated with metabolic syndrome. This study aimed to examine the association between circadian rhythm-disturbing factors and metabolic syndrome.
Methods:
We used data from the 7th and 8th Korea National Health and Nutrition Examination Survey conducted between 2016 and 2020, which surveyed 16,253 individuals. Circadian rhythm-disturbing factors were defined as follows: sleep duration outside the reference group (6–8 hours), irregular breakfast, shift work, and physical inactivity. The adjusted odds ratio (aOR) for metabolic syndrome was calculated based on the number of circadian rhythm-disturbing factors present in adults over the age of 19 years.
Results:
Among a total of 16,253 participants (mean age 48.2±15 years), metabolic syndrome was found in 5,237 participants (29.3 %). The participants were classified into three categories based on the number of circadian rhythm-disturbing factors as follows: 2,627 (15.6%) did not have any factors, 6,406 (38.13%) had one factor, and 7,220 (46.3%) had two or more factors. Participants with a single circadian rhythm-disturbing factor were 21% more likely to have metabolic syndrome (aOR, 1.21; 95% confidence interval [CI], 1.08–1.36), and participants with two or more factors were 27% more likely to have metabolic syndrome (aOR, 1.27; 95% CI, 1.12–1.43).
Conclusion
Circadian rhythm-disturbing factors were significantly associated with the prevalence of metabolic syndrome in Korean adults. This finding has potential clinical implications for maintaining circadian rhythms by avoiding certain factors to prevent metabolic syndrome. Further studies are required to confirm these findings.
7.The characteristics of patients who failed initial Kasai portoenterostomy and the long-term prognosis of those who underwent redo-Kasai: a retrospective observational study
Suhyeon HA ; Sujin GANG ; Jueun PARK ; Hyunhee KWON ; Dae Yeon KIM ; Seong Chul KIM ; Jung-Man NAMGOONG
Annals of Surgical Treatment and Research 2025;108(2):93-97
Purpose:
The purpose of this study was to determine the characteristics of patients with failed initial Kasai portoenterostomy (KP) and to compare the long-term prognosis of redo-KP with that of liver transplantation (LT) in these patients.
Methods:
The medical records of patients with biliary atresia (BA) who failed initial KP from 2010 to 2021 at a single center were retrospectively analyzed. KP failure was defined as persistent jaundice (total bilirubin concentration, ≥2.0 mg/dL) after KP or the performance of LT.
Results:
During the study period, 32 patients experienced initial KP failure, with 10 undergoing redo-KP and 22 undergoing LT. Redo-KP was successful in a minority of patients with failed initial KP, but the complications, particularly cholangitis, were more frequent in the redo-KP group. The long-term prognosis of redo-KP compared to LT showed that while some patients benefited from native liver survival after redo-KP, LT remains the more definitive solution for sustained liver function and survival in patients with BA.
Conclusion
The only factor differing significantly between patients who underwent redo-KP and LT after failed initial KP was complications of cholangitis. Redo-KP was successful in 4 of 10 patients with failed initial KP, suggesting that redo-KP may be a treatment option in patients with BA and failed initial KP.
8.Association between Circadian Rhythm-Disturbing Factors and Metabolic Syndrome in Korean Adults: Korea National Health and Nutrition Examination Survey (2016–2020)
Sujin LEE ; Junhee PARK ; Hyunjin CHO ; Jun Hyun YOO
Korean Journal of Family Medicine 2025;46(3):162-169
Background:
Circadian misalignment is associated with metabolic syndrome. This study aimed to examine the association between circadian rhythm-disturbing factors and metabolic syndrome.
Methods:
We used data from the 7th and 8th Korea National Health and Nutrition Examination Survey conducted between 2016 and 2020, which surveyed 16,253 individuals. Circadian rhythm-disturbing factors were defined as follows: sleep duration outside the reference group (6–8 hours), irregular breakfast, shift work, and physical inactivity. The adjusted odds ratio (aOR) for metabolic syndrome was calculated based on the number of circadian rhythm-disturbing factors present in adults over the age of 19 years.
Results:
Among a total of 16,253 participants (mean age 48.2±15 years), metabolic syndrome was found in 5,237 participants (29.3 %). The participants were classified into three categories based on the number of circadian rhythm-disturbing factors as follows: 2,627 (15.6%) did not have any factors, 6,406 (38.13%) had one factor, and 7,220 (46.3%) had two or more factors. Participants with a single circadian rhythm-disturbing factor were 21% more likely to have metabolic syndrome (aOR, 1.21; 95% confidence interval [CI], 1.08–1.36), and participants with two or more factors were 27% more likely to have metabolic syndrome (aOR, 1.27; 95% CI, 1.12–1.43).
Conclusion
Circadian rhythm-disturbing factors were significantly associated with the prevalence of metabolic syndrome in Korean adults. This finding has potential clinical implications for maintaining circadian rhythms by avoiding certain factors to prevent metabolic syndrome. Further studies are required to confirm these findings.
9.The characteristics of patients who failed initial Kasai portoenterostomy and the long-term prognosis of those who underwent redo-Kasai: a retrospective observational study
Suhyeon HA ; Sujin GANG ; Jueun PARK ; Hyunhee KWON ; Dae Yeon KIM ; Seong Chul KIM ; Jung-Man NAMGOONG
Annals of Surgical Treatment and Research 2025;108(2):93-97
Purpose:
The purpose of this study was to determine the characteristics of patients with failed initial Kasai portoenterostomy (KP) and to compare the long-term prognosis of redo-KP with that of liver transplantation (LT) in these patients.
Methods:
The medical records of patients with biliary atresia (BA) who failed initial KP from 2010 to 2021 at a single center were retrospectively analyzed. KP failure was defined as persistent jaundice (total bilirubin concentration, ≥2.0 mg/dL) after KP or the performance of LT.
Results:
During the study period, 32 patients experienced initial KP failure, with 10 undergoing redo-KP and 22 undergoing LT. Redo-KP was successful in a minority of patients with failed initial KP, but the complications, particularly cholangitis, were more frequent in the redo-KP group. The long-term prognosis of redo-KP compared to LT showed that while some patients benefited from native liver survival after redo-KP, LT remains the more definitive solution for sustained liver function and survival in patients with BA.
Conclusion
The only factor differing significantly between patients who underwent redo-KP and LT after failed initial KP was complications of cholangitis. Redo-KP was successful in 4 of 10 patients with failed initial KP, suggesting that redo-KP may be a treatment option in patients with BA and failed initial KP.
10.Association between Circadian Rhythm-Disturbing Factors and Metabolic Syndrome in Korean Adults: Korea National Health and Nutrition Examination Survey (2016–2020)
Sujin LEE ; Junhee PARK ; Hyunjin CHO ; Jun Hyun YOO
Korean Journal of Family Medicine 2025;46(3):162-169
Background:
Circadian misalignment is associated with metabolic syndrome. This study aimed to examine the association between circadian rhythm-disturbing factors and metabolic syndrome.
Methods:
We used data from the 7th and 8th Korea National Health and Nutrition Examination Survey conducted between 2016 and 2020, which surveyed 16,253 individuals. Circadian rhythm-disturbing factors were defined as follows: sleep duration outside the reference group (6–8 hours), irregular breakfast, shift work, and physical inactivity. The adjusted odds ratio (aOR) for metabolic syndrome was calculated based on the number of circadian rhythm-disturbing factors present in adults over the age of 19 years.
Results:
Among a total of 16,253 participants (mean age 48.2±15 years), metabolic syndrome was found in 5,237 participants (29.3 %). The participants were classified into three categories based on the number of circadian rhythm-disturbing factors as follows: 2,627 (15.6%) did not have any factors, 6,406 (38.13%) had one factor, and 7,220 (46.3%) had two or more factors. Participants with a single circadian rhythm-disturbing factor were 21% more likely to have metabolic syndrome (aOR, 1.21; 95% confidence interval [CI], 1.08–1.36), and participants with two or more factors were 27% more likely to have metabolic syndrome (aOR, 1.27; 95% CI, 1.12–1.43).
Conclusion
Circadian rhythm-disturbing factors were significantly associated with the prevalence of metabolic syndrome in Korean adults. This finding has potential clinical implications for maintaining circadian rhythms by avoiding certain factors to prevent metabolic syndrome. Further studies are required to confirm these findings.

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