1.Synergistic effects of L-arginine and argininosuccinate synthetase 1 in inducing apoptosis in hepatocellular carcinoma
Jin Sun KIM ; Won-Mook CHOI ; Ha-Il KIM ; Sung Won CHUNG ; Jonggi CHOI ; Danbi LEE ; Kang Mo KIM
Journal of Liver Cancer 2025;25(1):79-90
Background:
s/Aims: Hepatocellular carcinoma (HCC) is a malignant cancer with an increasing incidence worldwide. Although numerous efforts have been made to identify effective therapies for HCC, current strategies have limitations. We present a new approach for targeting L-arginine and argininosuccinate synthetase 1 (ASS1).
Methods:
ASS1 expression in HCC cell lines and primary hepatocytes was detected using polymerase chain reaction and western blotting. Proliferation, migration, signaling pathways, and nitric oxide production in HCC cell lines were measured using MTS, colony formation, wound healing, Western blot, and Griess assays.
Results:
ASS1 expression varied among the HCC cell lines, and cisplatin cytotoxicity was ASS1-dependent. L-arginine alone induced apoptosis in HCC cell lines, regardless of ASS1 expression; however, its effect was enhanced in ASS1-expressing HCC cell lines. Cisplatin cytotoxicity also increased, suggesting that L-arginine acts as a sensitizer to cisplatin in HCC cell lines. ASS1 and L-arginine produced nitric oxide and inhibited key proliferation- and survival-related signaling pathways such as PI3K/Akt and MAPK. Additionally, ASS1 and L-arginine reduced the expression of PKM1 and PKM2 in the glycolysis pathway.
Conclusions
Our study revealed that ASS1 and L-arginine exhibited anticancer effects in HCC and sensitized cisplatin-resistant HCC cells to chemotherapy. The combination of ASS1 and L-arginine significantly enhanced the anticancer effects, even in HCC cell lines with low or absent ASS1 expression. These findings highlight the critical roles of arginine and ASS1 in HCC and suggest that increasing arginine availability could be a promising therapeutic strategy.
2.Long-Term Incidence of Gastrointestinal Bleeding Following Ischemic Stroke
Jun Yup KIM ; Beom Joon KIM ; Jihoon KANG ; Do Yeon KIM ; Moon-Ku HAN ; Seong-Eun KIM ; Heeyoung LEE ; Jong-Moo PARK ; Kyusik KANG ; Soo Joo LEE ; Jae Guk KIM ; Jae-Kwan CHA ; Dae-Hyun KIM ; Tai Hwan PARK ; Kyungbok LEE ; Hong-Kyun PARK ; Yong-Jin CHO ; Keun-Sik HONG ; Kang-Ho CHOI ; Joon-Tae KIM ; Dong-Eog KIM ; Jay Chol CHOI ; Mi-Sun OH ; Kyung-Ho YU ; Byung-Chul LEE ; Kwang-Yeol PARK ; Ji Sung LEE ; Sujung JANG ; Jae Eun CHAE ; Juneyoung LEE ; Min-Surk KYE ; Philip B. GORELICK ; Hee-Joon BAE ;
Journal of Stroke 2025;27(1):102-112
Background:
and Purpose Previous research on patients with acute ischemic stroke (AIS) has shown a 0.5% incidence of major gastrointestinal bleeding (GIB) requiring blood transfusion during hospitalization. The existing literature has insufficiently explored the long-term incidence in this population despite the decremental impact of GIB on stroke outcomes.
Methods:
We analyzed the data from a cohort of patients with AIS admitted to 14 hospitals as part of a nationwide multicenter prospective stroke registry between 2011 and 2013. These patients were followed up for up to 6 years. The occurrence of major GIB events, defined as GIB necessitating at least two units of blood transfusion, was tracked using the National Health Insurance Service claims data.
Results:
Among 10,818 patients with AIS (male, 59%; mean age, 68±13 years), 947 (8.8%) experienced 1,224 episodes of major GIB over a median follow-up duration of 3.1 years. Remarkably, 20% of 947 patients experienced multiple episodes of major GIB. The incidence peaked in the first month after AIS, reaching 19.2 per 100 person-years, and gradually decreased to approximately one-sixth of this rate by the 2nd year with subsequent stabilization. Multivariable analysis identified the following predictors of major GIB: anemia, estimated glomerular filtration rate <60 mL/min/1.73 m2 , and a 3-month modified Rankin Scale score of ≥4.
Conclusion
Patients with AIS are susceptible to major GIB, particularly in the first month after the onset of AIS, with the risk decreasing thereafter. Implementing preventive strategies may be important, especially for patients with anemia and impaired renal function at stroke onset and those with a disabling stroke.
3.Early Administration of Nelonemdaz May Improve the Stroke Outcomes in Patients With Acute Stroke
Jin Soo LEE ; Ji Sung LEE ; Seong Hwan AHN ; Hyun Goo KANG ; Tae-Jin SONG ; Dong-Ick SHIN ; Hee-Joon BAE ; Chang Hun KIM ; Sung Hyuk HEO ; Jae-Kwan CHA ; Yeong Bae LEE ; Eung Gyu KIM ; Man Seok PARK ; Hee-Kwon PARK ; Jinkwon KIM ; Sungwook YU ; Heejung MO ; Sung Il SOHN ; Jee Hyun KWON ; Jae Guk KIM ; Young Seo KIM ; Jay Chol CHOI ; Yang-Ha HWANG ; Keun Hwa JUNG ; Soo-Kyoung KIM ; Woo Keun SEO ; Jung Hwa SEO ; Joonsang YOO ; Jun Young CHANG ; Mooseok PARK ; Kyu Sun YUM ; Chun San AN ; Byoung Joo GWAG ; Dennis W. CHOI ; Ji Man HONG ; Sun U. KWON ;
Journal of Stroke 2025;27(2):279-283
4.Clinical applications of regional anesthesia in enhancing postoperative recovery: a narrative review
Journal of the Korean Medical Association 2025;68(1):47-51
Effective pain management during postoperative recovery is vital because it influences patient outcomes, reduces complications, and enhances overall satisfaction. Although opioids have been traditionally used, their adverse effects and dependency risks have prompted the exploration of alternative treatments. Intravenous patient-controlled analgesia (IV-PCA) has gained attention because it allows for flexible, selfmanaged pain relief and reduces the side effects of opioids.Current Concepts: Regional anesthesia/analgesia selectively blocks pain in specific body parts. It is a promising method for multimodal pain management and enhanced recovery after surgery (ERAS) programs. This approach includes neuraxial (e.g., spinal and epidural anesthesia) and peripheral nerve blocking for localized pain relief. Ultrasound-guided techniques have improved the precision and safety of regional anesthesia, expanding their use across various surgical procedures. By targeting specific nerves, regional anesthesia/analgesia can effectively minimize opioid requirements and reduce the risk of adverse reactions.Discussion and Conclusion: Although regional anesthesia/analgesia offers significant advantages, it requires specialized equipment and expertise, with single-injection approaches limited by duration. Continuous catheter techniques and pharmacological adjuncts are being explored to extend analgesia and manage rebound pain. Regional anesthesia/analgesia not only minimizes opioid use but also mitigates dependency risks and postoperative complications. In conclusion, regional anesthesia/analgesia delivers targeted pain relief, reduces opioid reliance, and promotes faster recovery. Advances in technology continue to expand their applications, supporting safer patient-centered recovery pathways. Ongoing research will refine its role in comprehensive pain management strategies and enhance postoperative outcomes in diverse surgical populations.
5.Regional anesthesia for rapid recovery after orthopedic surgery
Min Kyoung KIM ; Jin Sun KIM ; Hyun KANG
Journal of the Korean Medical Association 2025;68(1):20-28
Orthopedic surgery is becoming increasingly common, particularly among older adults, due to population aging and the rising incidence of degenerative conditions. Older patients frequently have multiple comorbidities, which elevate the risk of surgical complications. Effective pain management is crucial in facilitating recovery and reducing the likelihood of postoperative complications. This review examines the role of regional anesthesia in optimizing recovery outcomes for orthopedic patients.Current Concepts: Regional anesthesia significantly reduces opioid consumption, which in turn mitigates side effects such as nausea, vomiting, respiratory depression, and urinary retention. It also promotes early mobilization, which is crucial for functional recovery, and helps prevent complications such as deep vein thrombosis and muscle atrophy. Advanced techniques like local infiltration analgesia and motor-sparing blocks offer effective pain relief while preserving muscle strength. This not only facilitates faster rehabilitation but also reduces the length of hospital stays. These advantages underscore the importance of regional anesthesia in improving surgical outcomes and expediting recovery.Discussion and Conclusion: Regional anesthesia is crucial in improving recovery after orthopedic surgery by providing effective pain management, facilitating early mobilization, and minimizing complications. It is essential to customize the anesthetic approach based on the specific surgical procedure and the patient’s overall health to achieve optimal outcomes.
6.Clinical Practice Guidelines for Dementia: Recommendations for Cholinesterase Inhibitors and Memantine
Yeshin KIM ; Dong Woo KANG ; Geon Ha KIM ; Ko Woon KIM ; Hee-Jin KIM ; Seunghee NA ; Kee Hyung PARK ; Young Ho PARK ; Gihwan BYEON ; Jeewon SUH ; Joon Hyun SHIN ; YongSoo SHIM ; YoungSoon YANG ; Yoo Hyun UM ; Seong-il OH ; Sheng-Min WANG ; Bora YOON ; Sun Min LEE ; Juyoun LEE ; Jin San LEE ; Jae-Sung LIM ; Young Hee JUNG ; Juhee CHIN ; Hyemin JANG ; Miyoung CHOI ; Yun Jeong HONG ; Hak Young RHEE ; Jae-Won JANG ;
Dementia and Neurocognitive Disorders 2025;24(1):1-23
Background:
and Purpose: This clinical practice guideline provides evidence-based recommendations for treatment of dementia, focusing on cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists for Alzheimer’s disease (AD) and other types of dementia.
Methods:
Using the Population, Intervention, Comparison, Outcomes (PICO) framework, we developed key clinical questions and conducted systematic literature reviews. A multidisciplinary panel of experts, organized by the Korean Dementia Association, evaluated randomized controlled trials and observational studies. Recommendations were graded for evidence quality and strength using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology.
Results:
Three main recommendations are presented: (1) For AD, cholinesterase inhibitors (donepezil, rivastigmine, galantamine) are strongly recommended for improving cognition and daily function based on moderate evidence; (2) Cholinesterase inhibitors are conditionally recommended for vascular dementia and Parkinson’s disease dementia, with a strong recommendation for Lewy body dementia; (3) For moderate to severe AD, NMDA receptor antagonist (memantine) is strongly recommended, demonstrating significant cognitive and functional improvements. Both drug classes showed favorable safety profiles with manageable side effects.
Conclusions
This guideline offers standardized, evidence-based pharmacologic recommendations for dementia management, with specific guidance on cholinesterase inhibitors and NMDA receptor antagonists. It aims to support clinical decision-making and improve patient outcomes in dementia care. Further updates will address emerging treatments, including amyloid-targeting therapies, to reflect advances in dementia management.
7.Effects of Cognitive and Depressive Status on Empathy in Healthy Elderly, Amnestic MCI, and Dementia of the Alzheimer’s Type
Seonyeong YANG ; Sun Hwa LEE ; Jaeho KIM ; Soo-Jin CHO ; Yeonwook KANG
Dementia and Neurocognitive Disorders 2025;24(1):54-68
Background:
and Purpose: Empathy comprises cognitive and emotional components.However, the impairments in empathy among individuals with mild cognitive impairment (MCI) and dementia of the Alzheimer’s type (DAT) are not well understood, particularly in the context of depression, which may exacerbate these deficits. This study aimed to evaluate the effects of neurodegeneration and depression on empathetic abilities.
Methods:
The study included 31 healthy elderly (HE) individuals, 30 patients with amnestic multi-domain MCI (amMCI), and 30 patients with DAT. Empathy was assessed using the Korean-Multifaceted Empathy Test (K-MET), and the Interpersonal Response Index (IRI).Participants were classified as depressed or non-depressed using the Geriatric Depression Scale. A two-way MANOVA was conducted to examine differences in empathy based on group and depressive status.
Results:
A significant interaction between group and depressive status was found for both cognitive and emotional empathy on the K-MET, but not on the IRI. In the depressed group, cognitive empathy scores were lower in the order of HE, amMCI, and DAT. Similarly, in the non-depressed group, the HE group performed better than both amMCI and DAT, with no significant difference between the latter two. Regarding emotional empathy, the depressed HE group scored higher than both amMCI and DAT, with no significant difference between these groups. In the non-depressed group, emotional empathy declined in the order of HE, amMCI, and DAT.
Conclusions
These findings indicate that both neurodegeneration and depression significantly impair empathetic abilities, with declines in cognitive and emotional empathy evident at the MCI stage, regardless of depressive status.
8.Long-term Clinical Efficacy of Radiotherapy for Patients with Stage I-II Gastric Extranodal Marginal Zone B-Cell Lymphoma of Mucosa-Associated Lymphoid Tissue: A Retrospective Multi-institutional Study
Jae Uk JEONG ; Hyo Chun LEE ; Jin Ho SONG ; Keun Yong EOM ; Jin Hee KIM ; Yoo Kang KWAK ; Woo Chul KIM ; Sun Young LEE ; Jin Hwa CHOI ; Kang Kyu LEE ; Jong Hoon LEE
Cancer Research and Treatment 2025;57(2):570-579
Purpose:
This study aimed to evaluate long-term treatment outcomes in patients with localized gastric mucosa-associated lymphoid tissue (MALT) lymphoma treated with radiotherapy (RT).
Materials and Methods:
A total of 229 patients who received RT in 10 tertiary hospitals between 2010 and 2019 were included in this multicenter analysis. Response after RT was based on esophagogastroduodenoscopy after RT. Locoregional relapse-free survival (LRFS) and disease-free survival (DFS), and overall survival (OS) were evaluated.
Results:
After a median follow-up time of 93.2 months, 5-year LRFS, DFS, and OS rates were 92.8%, 90.4%, and 96.1%, respectively. LRFS, DFS, and OS rates at 10 years were 90.3%, 87.7%, and 92.8%, respectively. Of 229 patients, 228 patients (99.6%) achieved complete remission after RT. Five-year LRFS was significantly lower in patients with stage IIE than in those with stage IE (77.4% vs. 94.2%, p=0.047). Patients with age ≥ 60 had significantly lower LRFS than patients with age < 60 (89.3% vs. 95.1%, p=0.003). In the multivariate analysis, old age (≥ 60 years) was a poor prognostic factor for LRFS (hazard ratio, 3.72; confidence interval, 1.38 to 10.03; p=0.009). Grade 2 or higher gastritis was reported in 69 patients (30.1%). Secondary malignancies including gastric adenocarcinoma, malignant lymphoma, lung cancer, breast cancer, and prostate cancer were observed in 11 patients (4.8%) after RT.
Conclusion
Patients treated with RT for localized gastric MALT lymphoma showed favorable 10-year outcomes. Radiation therapy is an effective treatment without an increased risk of secondary cancer. The toxicity for RT to the stomach is not high.
9.The Cancer Clinical Library Database (CCLD) from the Korea-Clinical Data Utilization Network for Research Excellence (K-CURE) Project
Sangwon LEE ; Yeon Ho CHOI ; Hak Min KIM ; Min Ah HONG ; Phillip PARK ; In Hae KWAK ; Ye Ji KANG ; Kui Son CHOI ; Hyun-Joo KONG ; Hyosung CHA ; Hyun-Jin KIM ; Kwang Sun RYU ; Young Sang JEON ; Hwanhee KIM ; Jip Min JUNG ; Jeong-Soo IM ; Heejung CHAE
Cancer Research and Treatment 2025;57(1):19-27
The common data model (CDM) has found widespread application in healthcare studies, but its utilization in cancer research has been limited. This article describes the development and implementation strategy for Cancer Clinical Library Databases (CCLDs), which are standardized cancer-specific databases established under the Korea-Clinical Data Utilization Network for Research Excellence (K-CURE) project by the Korean Ministry of Health and Welfare. Fifteen leading hospitals and fourteen academic associations in Korea are engaged in constructing CCLDs for 10 primary cancer types. For each cancer type-specific CCLD, cancer data experts determine key clinical data items essential for cancer research, standardize these items across cancer types, and create a standardized schema. Comprehensive clinical records covering diagnosis, treatment, and outcomes, with annual updates, are collected for each cancer patient in the target population, and quality control is based on six-sigma standards. To protect patient privacy, CCLDs follow stringent data security guidelines by pseudonymizing personal identification information and operating within a closed analysis environment. Researchers can apply for access to CCLD data through the K-CURE portal, which is subject to Institutional Review Board and Data Review Board approval. The CCLD is considered a pioneering standardized cancer-specific database, significantly representing Korea’s cancer data. It is expected to overcome limitations of previous CDMs and provide a valuable resource for multicenter cancer research in Korea.
10.Synergistic effects of L-arginine and argininosuccinate synthetase 1 in inducing apoptosis in hepatocellular carcinoma
Jin Sun KIM ; Won-Mook CHOI ; Ha-Il KIM ; Sung Won CHUNG ; Jonggi CHOI ; Danbi LEE ; Kang Mo KIM
Journal of Liver Cancer 2025;25(1):79-90
Background:
s/Aims: Hepatocellular carcinoma (HCC) is a malignant cancer with an increasing incidence worldwide. Although numerous efforts have been made to identify effective therapies for HCC, current strategies have limitations. We present a new approach for targeting L-arginine and argininosuccinate synthetase 1 (ASS1).
Methods:
ASS1 expression in HCC cell lines and primary hepatocytes was detected using polymerase chain reaction and western blotting. Proliferation, migration, signaling pathways, and nitric oxide production in HCC cell lines were measured using MTS, colony formation, wound healing, Western blot, and Griess assays.
Results:
ASS1 expression varied among the HCC cell lines, and cisplatin cytotoxicity was ASS1-dependent. L-arginine alone induced apoptosis in HCC cell lines, regardless of ASS1 expression; however, its effect was enhanced in ASS1-expressing HCC cell lines. Cisplatin cytotoxicity also increased, suggesting that L-arginine acts as a sensitizer to cisplatin in HCC cell lines. ASS1 and L-arginine produced nitric oxide and inhibited key proliferation- and survival-related signaling pathways such as PI3K/Akt and MAPK. Additionally, ASS1 and L-arginine reduced the expression of PKM1 and PKM2 in the glycolysis pathway.
Conclusions
Our study revealed that ASS1 and L-arginine exhibited anticancer effects in HCC and sensitized cisplatin-resistant HCC cells to chemotherapy. The combination of ASS1 and L-arginine significantly enhanced the anticancer effects, even in HCC cell lines with low or absent ASS1 expression. These findings highlight the critical roles of arginine and ASS1 in HCC and suggest that increasing arginine availability could be a promising therapeutic strategy.

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