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.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.
3.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.
4.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.
5.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.
6.Comparison of Monthly Characteristics of Adolescent Suicide Attempts Before, During and After COVID-19
Sujin YOO ; Hanjin CHO ; Boram CHAE ; Han Na KIM ; Ju Yeon JEE ; Ho-Kyoung YOON
Korean Journal of Psychosomatic Medicine 2024;32(2):64-69
Objectives:
:This study aimed to investigate the monthly characteristics of suicide attempts among adolescents considering the impact of the COVID-19 pandemic.
Methods:
:From 2018 to 2023, patients who arrived at Korea University Ansan Hospital’s emergency depart-ment following a suicide attempt were categorized by age, with adolescents defined as those aged 18 and below.These patients were then compared across three periods: pre COVID-19, COVID-19 period, and post COVID-19 periods.
Results:
:From January 2018 to December 2023, a total of 3,008 patients who attempted suicide visited the emergency room. Among them, 333 (11.1%) were adolescents. In the overall sample, the proportion of suicide attempts in January increased during the COVID-19 period compared to the pre-COVID-19 period, while the proportion in September decreased. Among adolescents, the proportion of suicide attempts in August decreased after COVID-19 compared to before.
Conclusions
:Our findings highlight a concerning increase in suicide attempts among teenagers, showing a cor-relation with the academic semester after COVID-19 pandemic. Understanding and addressing this trend are paramount for effective suicide risk management strategies moving forward.
7.Comparison of Monthly Characteristics of Adolescent Suicide Attempts Before, During and After COVID-19
Sujin YOO ; Hanjin CHO ; Boram CHAE ; Han Na KIM ; Ju Yeon JEE ; Ho-Kyoung YOON
Korean Journal of Psychosomatic Medicine 2024;32(2):64-69
Objectives:
:This study aimed to investigate the monthly characteristics of suicide attempts among adolescents considering the impact of the COVID-19 pandemic.
Methods:
:From 2018 to 2023, patients who arrived at Korea University Ansan Hospital’s emergency depart-ment following a suicide attempt were categorized by age, with adolescents defined as those aged 18 and below.These patients were then compared across three periods: pre COVID-19, COVID-19 period, and post COVID-19 periods.
Results:
:From January 2018 to December 2023, a total of 3,008 patients who attempted suicide visited the emergency room. Among them, 333 (11.1%) were adolescents. In the overall sample, the proportion of suicide attempts in January increased during the COVID-19 period compared to the pre-COVID-19 period, while the proportion in September decreased. Among adolescents, the proportion of suicide attempts in August decreased after COVID-19 compared to before.
Conclusions
:Our findings highlight a concerning increase in suicide attempts among teenagers, showing a cor-relation with the academic semester after COVID-19 pandemic. Understanding and addressing this trend are paramount for effective suicide risk management strategies moving forward.
8.Clinical Characteristics, Diagnosis, and Treatment of Thyroid Stimulating Hormone-Secreting Pituitary Neuroendocrine Tumor (TSH PitNET): A Single-Center Experience
Jung HEO ; Yeon-Lim SUH ; Se Hoon KIM ; Doo-Sik KONG ; Do-Hyun NAM ; Won-Jae LEE ; Sung Tae KIM ; Sang Duk HONG ; Sujin RYU ; You-Bin LEE ; Gyuri KIM ; Sang-Man JIN ; Jae Hyeon KIM ; Kyu Yeon HUR
Endocrinology and Metabolism 2024;39(2):387-396
Background:
Thyroid-stimulating hormone (TSH)-secreting pituitary neuroendocrine tumor (TSH PitNET) is a rare subtype of PitNET. We investigated the comprehensive characteristics and outcomes of TSH PitNET cases from a single medical center. Also, we compared diagnostic methods to determine which showed superior sensitivity.
Methods:
A total of 17 patients diagnosed with TSH PitNET after surgery between 2002 and 2022 in Samsung Medical Center was retrospectively reviewed. Data on comprehensive characteristics and treatment outcomes were collected. The sensitivities of diagnostic methods were compared.
Results:
Seven were male (41%), and the median age at diagnosis was 42 years (range, 21 to 65); the median follow-up duration was 37.4 months. The most common (59%) initial presentation was hyperthyroidism-related symptoms. Hormonal co-secretion was present in four (23%) patients. Elevated serum alpha-subunit (α-SU) showed the greatest diagnostic sensitivity (91%), followed by blunted response at thyrotropin-releasing hormone (TRH) stimulation (80%) and elevated sex hormone binding globulin (63%). Fourteen (82%) patients had macroadenoma, and a specimen of one patient with heavy calcification was negative for TSH. Among 15 patients who were followed up for more than 6 months, 10 (67%) achieved hormonal and structural remission within 6 months postoperatively. A case of growth hormone (GH)/TSH/prolactin (PRL) co-secreting mixed gangliocytoma-pituitary adenoma (MGPA) was discovered.
Conclusion
The majority of the TSH PitNET cases was macroadenoma, and 23% showed hormone co-secretion. A rare case of GH/TSH/PRL co-secreting MGPA was discovered. Serum α-SU and TRH stimulation tests showed great diagnostic sensitivity. Careful consideration is needed in diagnosing TSH PitNET. Achieving remission requires complete tumor resection. In case of nonremission, radiotherapy or medical therapy can improve the long-term remission rate.
9.Validation of the Karolinska Sleepiness Scale in Korean
Sungkyoung SHIN ; Sujin LEE ; Su Jung CHOI ; Eun Yeon JOO ; Sooyeon SUH
Journal of Clinical Neurology 2024;20(5):501-508
Background:
and Purpose The Karolinska Sleepiness Scale (KSS) is widely used for assessing current level of sleepiness, but it has not been validated in South Korea. This study aimed to validate the KSS using the Stanford Sleepiness Scale (SSS), polysomnography (PSG), and electroencephalography (EEG).
Methods:
The sample consisted of 27 adult participants in this study aged 40.5±7.7 years (mean±standard deviation) and included 22 males. They completed questionnaires and underwent EEG recording and overnight PSG. The KSS was completed from 18:00 to 24:00 every 2 hours and following PSG (at 07:00). KSS scores changed over time and in particular increased with the time since waking, with the score peaking at 24:00.
Results:
Convergent validity of the KSS was verified by performing a Spearman correlation analysis between the KSS and SSS (r=0.742, p<0.01). Concurrent validity of the KSS was verified by performing a Spearman correlation analysis between the KSS administered before sleep and the sleep onset latency measured using PSG (r=-0.456, p<0.05). Alpha waves were measured 5 minutes before administering the KSS, and the KSS scores were compared with these alpha waves. There were no significant correlations observed between the KSS scores and alpha waves measured in the left occipital area (O1), left frontal area (F3), or left central area (C3). In addition, Spearman correlation analyses of the difference between KSS scores and alpha waves measured at O1, F3, and C3 produced no significant results.
Conclusions
This study verified the convergent validity and concurrent validity of the KSS, and confirmed the capabilities of this scale in assessing sleepiness changes over time.
10.Comparison of Monthly Characteristics of Adolescent Suicide Attempts Before, During and After COVID-19
Sujin YOO ; Hanjin CHO ; Boram CHAE ; Han Na KIM ; Ju Yeon JEE ; Ho-Kyoung YOON
Korean Journal of Psychosomatic Medicine 2024;32(2):64-69
Objectives:
:This study aimed to investigate the monthly characteristics of suicide attempts among adolescents considering the impact of the COVID-19 pandemic.
Methods:
:From 2018 to 2023, patients who arrived at Korea University Ansan Hospital’s emergency depart-ment following a suicide attempt were categorized by age, with adolescents defined as those aged 18 and below.These patients were then compared across three periods: pre COVID-19, COVID-19 period, and post COVID-19 periods.
Results:
:From January 2018 to December 2023, a total of 3,008 patients who attempted suicide visited the emergency room. Among them, 333 (11.1%) were adolescents. In the overall sample, the proportion of suicide attempts in January increased during the COVID-19 period compared to the pre-COVID-19 period, while the proportion in September decreased. Among adolescents, the proportion of suicide attempts in August decreased after COVID-19 compared to before.
Conclusions
:Our findings highlight a concerning increase in suicide attempts among teenagers, showing a cor-relation with the academic semester after COVID-19 pandemic. Understanding and addressing this trend are paramount for effective suicide risk management strategies moving forward.

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