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.Elimusertib, a Novel ATR Inhibitor, Induces Anti-tumor Effects through Replication Catastrophe in Breast Cancers
Mudong KIM ; Ahrum MIN ; Sohyeon KIM ; Seongyeong KIM ; Yu-jin KIM ; Sujin HAM ; Miso LEE ; Eunice Yoojin LEE ; Jinyong KIM ; Dae-Won LEE ; Kyung-Hun LEE ; Seock-Ah IM
Cancer Research and Treatment 2026;58(1):159-174
Purpose:
Sustained cell proliferation and cell cycle acceleration in cancer cells inherently increase DNA damage, which interferes with homeostatic replication and transcription. Ataxia telangiectasia and Rad3-related (ATR) is crucial for initiation of the DNA damage response, and ATR inhibitors, such as elimusertib, induce increased replication stress and DNA damage. We investigated the anti-tumor effects of elimusertib and its mechanism of action in relation to replication stress.
Materials and Methods:
Anti-tumor effects were evaluated by MTT assay and colony formation assay in breast cancer cell lines in vitro, in breast cancer cell xenografts in vivo, and in patient-derived xenograft models. Cell cycle was assessed by flow cytometry and BrdU assay was used to measure replicating cells and S-phase progression. Alkaline and neutral comet assay was used to measure single and double-stranded DNA damages, respectively.
Results:
Elimusertib delayed S-phase progression in MDA-MB-453 and MDA-MB-231 cells and induced caspase-7–dependent apoptosis. Furthermore, the increase in sub-G1 population in the fluorescence-activated cell sorting analysis and Annexin V assay also confirmed apoptotic cell death. In the BrdU assay, single-stranded DNA (ssDNA) increased in sensitive cells and aberrant ssDNA induced DNA damage in S-phase and eventually caused replication catastrophe. Finally, these anti-tumor effects were proven in in vivo xenograft and patient-derived xenograft models.
Conclusion
Elimusertib had anti-tumor effects and induced replication catastrophe in breast cancer cells with a high replication rate. Moreover, cells under high DNA replication stress were sensitive to elimusertib. Further studies and treatment strategies with elimusertib are warranted for cancers with a high replication rate.
3.Pericapsular Nerve Group Block with Periarticular Injection for Pain Management after Total Hip Arthroplasty: A Randomized Controlled Trial
Hun Sik CHO ; Bo Ra LEE ; Hyuck Min KWON ; Jun Young PARK ; Hyeong Won HAM ; Woo-Suk LEE ; Kwan Kyu PARK ; Tae Sung LEE ; Yong Seon CHOI
Yonsei Medical Journal 2025;66(4):233-239
Purpose:
The purpose of this study was to compare the effectiveness of pericapsular nerve group (PENG) block with periarticular multimodal drug injection (PMDI) on postoperative pain management and surgical outcomes in patients who underwent total hip arthroplasty (THA). We hypothesized that PENG block with PMDI would exhibit superior effects on postoperative pain control after THA compared to PMDI alone.
Materials and Methods:
From April 2022 to February 2023, 58 patients who underwent THA were randomly assigned into two groups: PENG block with PMDI group (n=29) and PMDI-only group (n=29). Primary outcomes were postoperative numeric rating scale (NRS) at rest and during activity at 6, 24, and 48 hours postoperatively. Secondary outcomes were postoperative complications (nausea and vomiting), Richards-Campbell Sleep Questionnaire (RCSQ) score, length of hospital stay, Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index, Harris Hip Score (HHS), and total morphine usage after surgery.
Results:
There was no significant difference in postoperative pain for either resting NRS or active NRS. Postoperative nausea and vomiting, RCSQ score, length of hospital stay, WOMAC index, HHS, and total morphine usage exhibited no significant differences between the two groups.
Conclusion
Both groups showed no significant differences in postoperative pain and clinical outcomes, indicating that the addition of PENG block to PMDI does not improve pain management after applying the posterolateral approach of THA. PMDI alone during THA would be an efficient, fast, and safe method for managing postoperative pain. This article was registered with ClinicalTrials.gov (Gov ID: NCT05320913).
4.Pericapsular Nerve Group Block with Periarticular Injection for Pain Management after Total Hip Arthroplasty: A Randomized Controlled Trial
Hun Sik CHO ; Bo Ra LEE ; Hyuck Min KWON ; Jun Young PARK ; Hyeong Won HAM ; Woo-Suk LEE ; Kwan Kyu PARK ; Tae Sung LEE ; Yong Seon CHOI
Yonsei Medical Journal 2025;66(4):233-239
Purpose:
The purpose of this study was to compare the effectiveness of pericapsular nerve group (PENG) block with periarticular multimodal drug injection (PMDI) on postoperative pain management and surgical outcomes in patients who underwent total hip arthroplasty (THA). We hypothesized that PENG block with PMDI would exhibit superior effects on postoperative pain control after THA compared to PMDI alone.
Materials and Methods:
From April 2022 to February 2023, 58 patients who underwent THA were randomly assigned into two groups: PENG block with PMDI group (n=29) and PMDI-only group (n=29). Primary outcomes were postoperative numeric rating scale (NRS) at rest and during activity at 6, 24, and 48 hours postoperatively. Secondary outcomes were postoperative complications (nausea and vomiting), Richards-Campbell Sleep Questionnaire (RCSQ) score, length of hospital stay, Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index, Harris Hip Score (HHS), and total morphine usage after surgery.
Results:
There was no significant difference in postoperative pain for either resting NRS or active NRS. Postoperative nausea and vomiting, RCSQ score, length of hospital stay, WOMAC index, HHS, and total morphine usage exhibited no significant differences between the two groups.
Conclusion
Both groups showed no significant differences in postoperative pain and clinical outcomes, indicating that the addition of PENG block to PMDI does not improve pain management after applying the posterolateral approach of THA. PMDI alone during THA would be an efficient, fast, and safe method for managing postoperative pain. This article was registered with ClinicalTrials.gov (Gov ID: NCT05320913).
5.Pericapsular Nerve Group Block with Periarticular Injection for Pain Management after Total Hip Arthroplasty: A Randomized Controlled Trial
Hun Sik CHO ; Bo Ra LEE ; Hyuck Min KWON ; Jun Young PARK ; Hyeong Won HAM ; Woo-Suk LEE ; Kwan Kyu PARK ; Tae Sung LEE ; Yong Seon CHOI
Yonsei Medical Journal 2025;66(4):233-239
Purpose:
The purpose of this study was to compare the effectiveness of pericapsular nerve group (PENG) block with periarticular multimodal drug injection (PMDI) on postoperative pain management and surgical outcomes in patients who underwent total hip arthroplasty (THA). We hypothesized that PENG block with PMDI would exhibit superior effects on postoperative pain control after THA compared to PMDI alone.
Materials and Methods:
From April 2022 to February 2023, 58 patients who underwent THA were randomly assigned into two groups: PENG block with PMDI group (n=29) and PMDI-only group (n=29). Primary outcomes were postoperative numeric rating scale (NRS) at rest and during activity at 6, 24, and 48 hours postoperatively. Secondary outcomes were postoperative complications (nausea and vomiting), Richards-Campbell Sleep Questionnaire (RCSQ) score, length of hospital stay, Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index, Harris Hip Score (HHS), and total morphine usage after surgery.
Results:
There was no significant difference in postoperative pain for either resting NRS or active NRS. Postoperative nausea and vomiting, RCSQ score, length of hospital stay, WOMAC index, HHS, and total morphine usage exhibited no significant differences between the two groups.
Conclusion
Both groups showed no significant differences in postoperative pain and clinical outcomes, indicating that the addition of PENG block to PMDI does not improve pain management after applying the posterolateral approach of THA. PMDI alone during THA would be an efficient, fast, and safe method for managing postoperative pain. This article was registered with ClinicalTrials.gov (Gov ID: NCT05320913).
6.Pericapsular Nerve Group Block with Periarticular Injection for Pain Management after Total Hip Arthroplasty: A Randomized Controlled Trial
Hun Sik CHO ; Bo Ra LEE ; Hyuck Min KWON ; Jun Young PARK ; Hyeong Won HAM ; Woo-Suk LEE ; Kwan Kyu PARK ; Tae Sung LEE ; Yong Seon CHOI
Yonsei Medical Journal 2025;66(4):233-239
Purpose:
The purpose of this study was to compare the effectiveness of pericapsular nerve group (PENG) block with periarticular multimodal drug injection (PMDI) on postoperative pain management and surgical outcomes in patients who underwent total hip arthroplasty (THA). We hypothesized that PENG block with PMDI would exhibit superior effects on postoperative pain control after THA compared to PMDI alone.
Materials and Methods:
From April 2022 to February 2023, 58 patients who underwent THA were randomly assigned into two groups: PENG block with PMDI group (n=29) and PMDI-only group (n=29). Primary outcomes were postoperative numeric rating scale (NRS) at rest and during activity at 6, 24, and 48 hours postoperatively. Secondary outcomes were postoperative complications (nausea and vomiting), Richards-Campbell Sleep Questionnaire (RCSQ) score, length of hospital stay, Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index, Harris Hip Score (HHS), and total morphine usage after surgery.
Results:
There was no significant difference in postoperative pain for either resting NRS or active NRS. Postoperative nausea and vomiting, RCSQ score, length of hospital stay, WOMAC index, HHS, and total morphine usage exhibited no significant differences between the two groups.
Conclusion
Both groups showed no significant differences in postoperative pain and clinical outcomes, indicating that the addition of PENG block to PMDI does not improve pain management after applying the posterolateral approach of THA. PMDI alone during THA would be an efficient, fast, and safe method for managing postoperative pain. This article was registered with ClinicalTrials.gov (Gov ID: NCT05320913).
7.Pericapsular Nerve Group Block with Periarticular Injection for Pain Management after Total Hip Arthroplasty: A Randomized Controlled Trial
Hun Sik CHO ; Bo Ra LEE ; Hyuck Min KWON ; Jun Young PARK ; Hyeong Won HAM ; Woo-Suk LEE ; Kwan Kyu PARK ; Tae Sung LEE ; Yong Seon CHOI
Yonsei Medical Journal 2025;66(4):233-239
Purpose:
The purpose of this study was to compare the effectiveness of pericapsular nerve group (PENG) block with periarticular multimodal drug injection (PMDI) on postoperative pain management and surgical outcomes in patients who underwent total hip arthroplasty (THA). We hypothesized that PENG block with PMDI would exhibit superior effects on postoperative pain control after THA compared to PMDI alone.
Materials and Methods:
From April 2022 to February 2023, 58 patients who underwent THA were randomly assigned into two groups: PENG block with PMDI group (n=29) and PMDI-only group (n=29). Primary outcomes were postoperative numeric rating scale (NRS) at rest and during activity at 6, 24, and 48 hours postoperatively. Secondary outcomes were postoperative complications (nausea and vomiting), Richards-Campbell Sleep Questionnaire (RCSQ) score, length of hospital stay, Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index, Harris Hip Score (HHS), and total morphine usage after surgery.
Results:
There was no significant difference in postoperative pain for either resting NRS or active NRS. Postoperative nausea and vomiting, RCSQ score, length of hospital stay, WOMAC index, HHS, and total morphine usage exhibited no significant differences between the two groups.
Conclusion
Both groups showed no significant differences in postoperative pain and clinical outcomes, indicating that the addition of PENG block to PMDI does not improve pain management after applying the posterolateral approach of THA. PMDI alone during THA would be an efficient, fast, and safe method for managing postoperative pain. This article was registered with ClinicalTrials.gov (Gov ID: NCT05320913).
8.Clinical characteristics of toxoplasmosis patients in Korea: A retrospective study using health insurance review and assessment service data and electronic medical records
Do-Won HAM ; Bong-Kwang JUNG ; Ji-Hun SHIN ; Yong Joon KIM ; Kyoung Yul SEO ; Seung Mi LEE ; Jae Hyoung IM ; Jeong-Ran KWON ; Ho-Sung LEE ; Kyung-Won HWANG ; Eun-Hee SHIN
Parasites, Hosts and Diseases 2024;62(4):424-437
This study aimed to elucidate the clinical characteristics of patients diagnosed with toxoplasmosis in Korea. We collected and analyzed the specific research data of 5,917 patients from the Health Insurance Review and Assessment (HIRA; 2007–2020) and 533 electronic medical records (EMRs; 2003–2021) of Korean patients. The HIRA data showed that toxoplasmosis is an endemic disease that occurs constantly in Korea, with a large proportion of patients complaining of ocular symptoms. Of the 533 patients for whom EMR data were available, 54.6% were diagnosed with toxoplasmosis; ocular toxoplasmosis (35.7%), congenital toxoplasmosis (4.7%), cerebral toxoplasmosis (4.1%), pulmonary toxoplasmosis (0.4%), and toxoplasma hepatitis (0.6%), in order of frequency. In ocular cases, 54.4% of the patients had diverse ocular pathologies. Toxoplasmosis in Korea is characterized by a high frequency of ocular symptoms, most patients are adults, and 51.8% of patients with seropositivity were positive for IgG, suggesting prior infection. This study highlights that patients with ocular symptoms are included in the major diagnosis group for acquired toxoplasmosis in Korea.
9.Clinical characteristics of toxoplasmosis patients in Korea: A retrospective study using health insurance review and assessment service data and electronic medical records
Do-Won HAM ; Bong-Kwang JUNG ; Ji-Hun SHIN ; Yong Joon KIM ; Kyoung Yul SEO ; Seung Mi LEE ; Jae Hyoung IM ; Jeong-Ran KWON ; Ho-Sung LEE ; Kyung-Won HWANG ; Eun-Hee SHIN
Parasites, Hosts and Diseases 2024;62(4):424-437
This study aimed to elucidate the clinical characteristics of patients diagnosed with toxoplasmosis in Korea. We collected and analyzed the specific research data of 5,917 patients from the Health Insurance Review and Assessment (HIRA; 2007–2020) and 533 electronic medical records (EMRs; 2003–2021) of Korean patients. The HIRA data showed that toxoplasmosis is an endemic disease that occurs constantly in Korea, with a large proportion of patients complaining of ocular symptoms. Of the 533 patients for whom EMR data were available, 54.6% were diagnosed with toxoplasmosis; ocular toxoplasmosis (35.7%), congenital toxoplasmosis (4.7%), cerebral toxoplasmosis (4.1%), pulmonary toxoplasmosis (0.4%), and toxoplasma hepatitis (0.6%), in order of frequency. In ocular cases, 54.4% of the patients had diverse ocular pathologies. Toxoplasmosis in Korea is characterized by a high frequency of ocular symptoms, most patients are adults, and 51.8% of patients with seropositivity were positive for IgG, suggesting prior infection. This study highlights that patients with ocular symptoms are included in the major diagnosis group for acquired toxoplasmosis in Korea.
10.Clinical characteristics of toxoplasmosis patients in Korea: A retrospective study using health insurance review and assessment service data and electronic medical records
Do-Won HAM ; Bong-Kwang JUNG ; Ji-Hun SHIN ; Yong Joon KIM ; Kyoung Yul SEO ; Seung Mi LEE ; Jae Hyoung IM ; Jeong-Ran KWON ; Ho-Sung LEE ; Kyung-Won HWANG ; Eun-Hee SHIN
Parasites, Hosts and Diseases 2024;62(4):424-437
This study aimed to elucidate the clinical characteristics of patients diagnosed with toxoplasmosis in Korea. We collected and analyzed the specific research data of 5,917 patients from the Health Insurance Review and Assessment (HIRA; 2007–2020) and 533 electronic medical records (EMRs; 2003–2021) of Korean patients. The HIRA data showed that toxoplasmosis is an endemic disease that occurs constantly in Korea, with a large proportion of patients complaining of ocular symptoms. Of the 533 patients for whom EMR data were available, 54.6% were diagnosed with toxoplasmosis; ocular toxoplasmosis (35.7%), congenital toxoplasmosis (4.7%), cerebral toxoplasmosis (4.1%), pulmonary toxoplasmosis (0.4%), and toxoplasma hepatitis (0.6%), in order of frequency. In ocular cases, 54.4% of the patients had diverse ocular pathologies. Toxoplasmosis in Korea is characterized by a high frequency of ocular symptoms, most patients are adults, and 51.8% of patients with seropositivity were positive for IgG, suggesting prior infection. This study highlights that patients with ocular symptoms are included in the major diagnosis group for acquired toxoplasmosis in Korea.

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