1.6-Gingerol Induced Apoptosis and Cell Cycle Arrest in Glioma Cells via MnSOD and ERK Phosphorylation Modulation
Sher-Wei LIM ; Wei-Chung CHEN ; Huey-Jiun KO ; Yu-Feng SU ; Chieh-Hsin WU ; Fu-Long HUANG ; Chien-Feng LI ; Cheng Yu TSAI
Biomolecules & Therapeutics 2025;33(1):129-142
6-gingerol, a bioactive compound from ginger, has demonstrated promising anticancer properties across various cancer models by inducing apoptosis and inhibiting cell proliferation and invasion. In this study, we explore its mechanisms against glioblastoma multiforme (GBM), a notably aggressive and treatment-resistant brain tumor. We found that 6-gingerol crosses the blood-brain barrier more effectively than curcumin, enhancing its potential as a therapeutic agent for brain tumors. Our experiments show that 6-gingerol reduces cell proliferation and triggers apoptosis in GBM cell lines by disrupting cellular energy homeostasis. This process involves an increase in mitochondrial reactive oxygen species (mtROS) and a decrease in mitochondrial membrane potential, primarily due to the downregulation of manganese superoxide dismutase (MnSOD). Additionally, 6-gingerol reduces ERK phosphorylation by inhibiting EGFR and RAF, leading to G1 phase cell cycle arrest. These findings indicate that 6-gingerol promotes cell death in GBM cells by modulating MnSOD and ROS levels and arresting the cell cycle through the ERFR-RAF-1/MEK/ ERK signaling pathway, highlighting its potential as a therapeutic agent for GBM and setting the stage for future clinical research.
2.Factors Associated with Postoperative Recurrence in Stage I to IIIA Non–Small Cell Lung Cancer with Epidermal Growth Factor Receptor Mutation: Analysis of Korean National Population Data
Kyu Yean KIM ; Ho Cheol KIM ; Tae Jung KIM ; Hong Kwan KIM ; Mi Hyung MOON ; Kyongmin Sarah BECK ; Yang Gun SUH ; Chang Hoon SONG ; Jin Seok AHN ; Jeong Eun LEE ; Jae Hyun JEON ; Chi Young JUNG ; Jeong Su CHO ; Yoo Duk CHOI ; Seung Sik HWANG ; Chang Min CHOI ; Seung Hun JANG ; Jeong Uk LIM ;
Cancer Research and Treatment 2025;57(1):83-94
Purpose:
Recent development in perioperative treatment of resectable non–small cell lung cancer (NSCLC) have changed the landscape of early lung cancer management. The ADAURA trial has demonstrated the efficacy of adjuvant osimertinib treatment in resectable NSCLC patients; however, studies are required to show which subgroup of patients are at a high risk of relapse and require adjuvant epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor treatment. This study evaluated risk factors for postoperative relapse among patients who underwent complete resection.
Materials and Methods:
Data were obtained from the Korean Association for Lung Cancer Registry (KALC-R), a database created using a retrospective sampling survey by the Korean Central Cancer Registry (KCCR) and the Lung Cancer Registration Committee.
Results:
A total of 3,176 patients who underwent curative resection was evaluated. The mean observation time was approximately 35.4 months. Among stage I to IIIA NSCLC patients, the EGFR-mutant subgroup included 867 patients, and 75.2%, 11.2%, and 11.8% were classified as stage I, stage II, and stage III, respectively. Within the EGFR-mutant subgroup, 44 (5.1%) and 121 (14.0%) patients showed early and late recurrence, respectively. Multivariate analysis on association with postoperative relapse among the EGFR-mutant subgroup showed that age, pathologic N and TNM stages, pleural invasion status, and surgery type were independent significant factors.
Conclusion
Among the population that underwent complete resection for early NSCLC with EGFR mutation, patients with advanced stage, pleural invasion, or limited resection are more likely to show postoperative relapse.
3.6-Gingerol Induced Apoptosis and Cell Cycle Arrest in Glioma Cells via MnSOD and ERK Phosphorylation Modulation
Sher-Wei LIM ; Wei-Chung CHEN ; Huey-Jiun KO ; Yu-Feng SU ; Chieh-Hsin WU ; Fu-Long HUANG ; Chien-Feng LI ; Cheng Yu TSAI
Biomolecules & Therapeutics 2025;33(1):129-142
6-gingerol, a bioactive compound from ginger, has demonstrated promising anticancer properties across various cancer models by inducing apoptosis and inhibiting cell proliferation and invasion. In this study, we explore its mechanisms against glioblastoma multiforme (GBM), a notably aggressive and treatment-resistant brain tumor. We found that 6-gingerol crosses the blood-brain barrier more effectively than curcumin, enhancing its potential as a therapeutic agent for brain tumors. Our experiments show that 6-gingerol reduces cell proliferation and triggers apoptosis in GBM cell lines by disrupting cellular energy homeostasis. This process involves an increase in mitochondrial reactive oxygen species (mtROS) and a decrease in mitochondrial membrane potential, primarily due to the downregulation of manganese superoxide dismutase (MnSOD). Additionally, 6-gingerol reduces ERK phosphorylation by inhibiting EGFR and RAF, leading to G1 phase cell cycle arrest. These findings indicate that 6-gingerol promotes cell death in GBM cells by modulating MnSOD and ROS levels and arresting the cell cycle through the ERFR-RAF-1/MEK/ ERK signaling pathway, highlighting its potential as a therapeutic agent for GBM and setting the stage for future clinical research.
4.Factors Associated with Postoperative Recurrence in Stage I to IIIA Non–Small Cell Lung Cancer with Epidermal Growth Factor Receptor Mutation: Analysis of Korean National Population Data
Kyu Yean KIM ; Ho Cheol KIM ; Tae Jung KIM ; Hong Kwan KIM ; Mi Hyung MOON ; Kyongmin Sarah BECK ; Yang Gun SUH ; Chang Hoon SONG ; Jin Seok AHN ; Jeong Eun LEE ; Jae Hyun JEON ; Chi Young JUNG ; Jeong Su CHO ; Yoo Duk CHOI ; Seung Sik HWANG ; Chang Min CHOI ; Seung Hun JANG ; Jeong Uk LIM ;
Cancer Research and Treatment 2025;57(1):83-94
Purpose:
Recent development in perioperative treatment of resectable non–small cell lung cancer (NSCLC) have changed the landscape of early lung cancer management. The ADAURA trial has demonstrated the efficacy of adjuvant osimertinib treatment in resectable NSCLC patients; however, studies are required to show which subgroup of patients are at a high risk of relapse and require adjuvant epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor treatment. This study evaluated risk factors for postoperative relapse among patients who underwent complete resection.
Materials and Methods:
Data were obtained from the Korean Association for Lung Cancer Registry (KALC-R), a database created using a retrospective sampling survey by the Korean Central Cancer Registry (KCCR) and the Lung Cancer Registration Committee.
Results:
A total of 3,176 patients who underwent curative resection was evaluated. The mean observation time was approximately 35.4 months. Among stage I to IIIA NSCLC patients, the EGFR-mutant subgroup included 867 patients, and 75.2%, 11.2%, and 11.8% were classified as stage I, stage II, and stage III, respectively. Within the EGFR-mutant subgroup, 44 (5.1%) and 121 (14.0%) patients showed early and late recurrence, respectively. Multivariate analysis on association with postoperative relapse among the EGFR-mutant subgroup showed that age, pathologic N and TNM stages, pleural invasion status, and surgery type were independent significant factors.
Conclusion
Among the population that underwent complete resection for early NSCLC with EGFR mutation, patients with advanced stage, pleural invasion, or limited resection are more likely to show postoperative relapse.
5.6-Gingerol Induced Apoptosis and Cell Cycle Arrest in Glioma Cells via MnSOD and ERK Phosphorylation Modulation
Sher-Wei LIM ; Wei-Chung CHEN ; Huey-Jiun KO ; Yu-Feng SU ; Chieh-Hsin WU ; Fu-Long HUANG ; Chien-Feng LI ; Cheng Yu TSAI
Biomolecules & Therapeutics 2025;33(1):129-142
6-gingerol, a bioactive compound from ginger, has demonstrated promising anticancer properties across various cancer models by inducing apoptosis and inhibiting cell proliferation and invasion. In this study, we explore its mechanisms against glioblastoma multiforme (GBM), a notably aggressive and treatment-resistant brain tumor. We found that 6-gingerol crosses the blood-brain barrier more effectively than curcumin, enhancing its potential as a therapeutic agent for brain tumors. Our experiments show that 6-gingerol reduces cell proliferation and triggers apoptosis in GBM cell lines by disrupting cellular energy homeostasis. This process involves an increase in mitochondrial reactive oxygen species (mtROS) and a decrease in mitochondrial membrane potential, primarily due to the downregulation of manganese superoxide dismutase (MnSOD). Additionally, 6-gingerol reduces ERK phosphorylation by inhibiting EGFR and RAF, leading to G1 phase cell cycle arrest. These findings indicate that 6-gingerol promotes cell death in GBM cells by modulating MnSOD and ROS levels and arresting the cell cycle through the ERFR-RAF-1/MEK/ ERK signaling pathway, highlighting its potential as a therapeutic agent for GBM and setting the stage for future clinical research.
6.Factors Associated with Postoperative Recurrence in Stage I to IIIA Non–Small Cell Lung Cancer with Epidermal Growth Factor Receptor Mutation: Analysis of Korean National Population Data
Kyu Yean KIM ; Ho Cheol KIM ; Tae Jung KIM ; Hong Kwan KIM ; Mi Hyung MOON ; Kyongmin Sarah BECK ; Yang Gun SUH ; Chang Hoon SONG ; Jin Seok AHN ; Jeong Eun LEE ; Jae Hyun JEON ; Chi Young JUNG ; Jeong Su CHO ; Yoo Duk CHOI ; Seung Sik HWANG ; Chang Min CHOI ; Seung Hun JANG ; Jeong Uk LIM ;
Cancer Research and Treatment 2025;57(1):83-94
Purpose:
Recent development in perioperative treatment of resectable non–small cell lung cancer (NSCLC) have changed the landscape of early lung cancer management. The ADAURA trial has demonstrated the efficacy of adjuvant osimertinib treatment in resectable NSCLC patients; however, studies are required to show which subgroup of patients are at a high risk of relapse and require adjuvant epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor treatment. This study evaluated risk factors for postoperative relapse among patients who underwent complete resection.
Materials and Methods:
Data were obtained from the Korean Association for Lung Cancer Registry (KALC-R), a database created using a retrospective sampling survey by the Korean Central Cancer Registry (KCCR) and the Lung Cancer Registration Committee.
Results:
A total of 3,176 patients who underwent curative resection was evaluated. The mean observation time was approximately 35.4 months. Among stage I to IIIA NSCLC patients, the EGFR-mutant subgroup included 867 patients, and 75.2%, 11.2%, and 11.8% were classified as stage I, stage II, and stage III, respectively. Within the EGFR-mutant subgroup, 44 (5.1%) and 121 (14.0%) patients showed early and late recurrence, respectively. Multivariate analysis on association with postoperative relapse among the EGFR-mutant subgroup showed that age, pathologic N and TNM stages, pleural invasion status, and surgery type were independent significant factors.
Conclusion
Among the population that underwent complete resection for early NSCLC with EGFR mutation, patients with advanced stage, pleural invasion, or limited resection are more likely to show postoperative relapse.
7.ChatGPT Predicts In-Hospital All-Cause Mortality for Sepsis: In-Context Learning with the Korean Sepsis Alliance Database
Namkee OH ; Won Chul CHA ; Jun Hyuk SEO ; Seong-Gyu CHOI ; Jong Man KIM ; Chi Ryang CHUNG ; Gee Young SUH ; Su Yeon LEE ; Dong Kyu OH ; Mi Hyeon PARK ; Chae-Man LIM ; Ryoung-Eun KO ;
Healthcare Informatics Research 2024;30(3):266-276
Objectives:
Sepsis is a leading global cause of mortality, and predicting its outcomes is vital for improving patient care. This study explored the capabilities of ChatGPT, a state-of-the-art natural language processing model, in predicting in-hospital mortality for sepsis patients.
Methods:
This study utilized data from the Korean Sepsis Alliance (KSA) database, collected between 2019 and 2021, focusing on adult intensive care unit (ICU) patients and aiming to determine whether ChatGPT could predict all-cause mortality after ICU admission at 7 and 30 days. Structured prompts enabled ChatGPT to engage in in-context learning, with the number of patient examples varying from zero to six. The predictive capabilities of ChatGPT-3.5-turbo and ChatGPT-4 were then compared against a gradient boosting model (GBM) using various performance metrics.
Results:
From the KSA database, 4,786 patients formed the 7-day mortality prediction dataset, of whom 718 died, and 4,025 patients formed the 30-day dataset, with 1,368 deaths. Age and clinical markers (e.g., Sequential Organ Failure Assessment score and lactic acid levels) showed significant differences between survivors and non-survivors in both datasets. For 7-day mortality predictions, the area under the receiver operating characteristic curve (AUROC) was 0.70–0.83 for GPT-4, 0.51–0.70 for GPT-3.5, and 0.79 for GBM. The AUROC for 30-day mortality was 0.51–0.59 for GPT-4, 0.47–0.57 for GPT-3.5, and 0.76 for GBM. Zero-shot predictions using GPT-4 for mortality from ICU admission to day 30 showed AUROCs from the mid-0.60s to 0.75 for GPT-4 and mainly from 0.47 to 0.63 for GPT-3.5.
Conclusions
GPT-4 demonstrated potential in predicting short-term in-hospital mortality, although its performance varied across different evaluation metrics.
8.Risk Factors for the Mortality of Patients With Coronavirus Disease 2019Requiring Extracorporeal Membrane Oxygenation in a Non-Centralized Setting: A Nationwide Study
Tae Wan KIM ; Won-Young KIM ; Sunghoon PARK ; Su Hwan LEE ; Onyu PARK ; Taehwa KIM ; Hye Ju YEO ; Jin Ho JANG ; Woo Hyun CHO ; Jin-Won HUH ; Sang-Min LEE ; Chi Ryang CHUNG ; Jongmin LEE ; Jung Soo KIM ; Sung Yoon LIM ; Ae-Rin BAEK ; Jung-Wan YOO ; Ho Cheol KIM ; Eun Young CHOI ; Chul PARK ; Tae-Ok KIM ; Do Sik MOON ; Song-I LEE ; Jae Young MOON ; Sun Jung KWON ; Gil Myeong SEONG ; Won Jai JUNG ; Moon Seong BAEK ;
Journal of Korean Medical Science 2024;39(8):e75-
Background:
Limited data are available on the mortality rates of patients receiving extracorporeal membrane oxygenation (ECMO) support for coronavirus disease 2019 (COVID-19). We aimed to analyze the relationship between COVID-19 and clinical outcomes for patients receiving ECMO.
Methods:
We retrospectively investigated patients with COVID-19 pneumonia requiring ECMO in 19 hospitals across Korea from January 1, 2020 to August 31, 2021. The primary outcome was the 90-day mortality after ECMO initiation. We performed multivariate analysis using a logistic regression model to estimate the odds ratio (OR) of 90-day mortality. Survival differences were analyzed using the Kaplan–Meier (KM) method.
Results:
Of 127 patients with COVID-19 pneumonia who received ECMO, 70 patients (55.1%) died within 90 days of ECMO initiation. The median age was 64 years, and 63% of patients were male. The incidence of ECMO was increased with age but was decreased after 70 years of age. However, the survival rate was decreased linearly with age. In multivariate analysis, age (OR, 1.048; 95% confidence interval [CI], 1.010–1.089; P = 0.014) and receipt of continuous renal replacement therapy (CRRT) (OR, 3.069; 95% CI, 1.312–7.180; P = 0.010) were significantly associated with an increased risk of 90-day mortality. KM curves showed significant differences in survival between groups according to age (65 years) (log-rank P = 0.021) and receipt of CRRT (log-rank P = 0.004).
Conclusion
Older age and receipt of CRRT were associated with higher mortality rates among patients with COVID-19 who received ECMO.
9.The role of triglyceride-glucose index in the prediction of the development of hypertension – findings from a community cohort in Singapore
Jonathon Khoo ; Serena Low ; Bastari Irwan ; Justin Tang ; Chee Fang Sum ; Tavintharan Subramaniam ; Su Chi Lim
Journal of the ASEAN Federation of Endocrine Societies 2023;38(1):62-67
Objectives:
Triglyceride-glucose index (TyGI) is an emerging surrogate marker of insulin resistance. We aim to explore the role of triglyceride-glucose index in the prediction of the development of hypertension.
Methodology:
nducted a retrospective cohort study that included 3,183 study participants identified from a community health screening programme who had no baseline hypertension and were then followed up after an average of 1.7 years. Cox proportional-hazard model was used to assess the association between risk of incident hypertension and TyGI in quartiles, while adjusting for demographics and clinical characteristics.
Results:
Hypertension occurred in 363 study participants (11.4%). Those who developed hypertension had higher TyGI [8.6 (IQR 8.2-9.0)] than those who did not [8.2 (IQR 8.0-8.7)] (p<0.001). Significant association between TyGI and hypertension was observed in both the unadjusted and proportional hazard model [Quartile (Q)2, p=0.010; Q3, p<0.001 and Q4, p<0.001] and the model that adjusted for demographics (Q2, p=0.016; Q3, p=0.003; Q4, p<0.001). In the model adjusted for clinical covariates, the hazard of developing hypertension remained higher in TyGI Q4 compared to TyGI Q1(Hazard Ratio=2.57; 95% Confidence Interval: 1.71, 3.87). Increasing triglyceride-glucose index accounted for 16.4% of the association between increasing BMI and incident hypertension, after adjusting for age, gender, ethnicity and baseline HDL cholesterol (p<0.001).
Conclusion
Triglyceride-glucose index was an independent predictor of the development of hypertension. It may potentially be used as an inexpensive indicator to predict the development of hypertension and risk-stratify individuals to aid management in clinical practice.
Diabetes Mellitus
;
Triglycerides
;
Hypertension
;
Screening
10.Five-Year Overall Survival and Prognostic Factors in Patients with Lung Cancer: Results from the Korean Association of Lung Cancer Registry (KALC-R) 2015
Da Som JEON ; Ho Cheol KIM ; Se Hee KIM ; Tae-Jung KIM ; Hong Kwan KIM ; Mi Hyung MOON ; Kyongmin Sarah BECK ; Yang-Gun SUH ; Changhoon SONG ; Jin Seok AHN ; Jeong Eun LEE ; Jeong Uk LIM ; Jae Hyun JEON ; Kyu-Won JUNG ; Chi Young JUNG ; Jeong Su CHO ; Yoo-Duk CHOI ; Seung-Sik HWANG ; Chang-Min CHOI ; ;
Cancer Research and Treatment 2023;55(1):103-111
Purpose:
This study aimed to provide the clinical characteristics, prognostic factors, and 5-year relative survival rates of lung cancer diagnosed in 2015.
Materials and Methods:
The demographic risk factors of lung cancer were calculated using the KALC-R (Korean Association of Lung Cancer Registry) cohort in 2015, with survival follow-up until December 31, 2020. The 5-year relative survival rates were estimated using Ederer II methods, and the general population data used the death rate adjusted for sex and age published by the Korea Statistical Information Service from 2015 to 2020.
Results:
We enrolled 2,657 patients with lung cancer who were diagnosed in South Korea in 2015. Of all patients, 2,098 (79.0%) were diagnosed with non–small cell lung cancer (NSCLC) and 345 (13.0%) were diagnosed with small cell lung cancer (SCLC), respectively. Old age, poor performance status, and advanced clinical stage were independent risk factors for both NSCLC and SCLC. In addition, the 5-year relative survival rate declined with advanced stage in both NSCLC (82%, 59%, 16%, 10% as the stage progressed) and SCLC (16%, 4% as the stage progressed). In patients with stage IV adenocarcinoma, the 5-year relative survival rate was higher in the presence of epidermal growth factor receptor (EGFR) mutation (19% vs. 11%) or anaplastic lymphoma kinase (ALK) translocation (38% vs. 11%).
Conclusion
In this Korean nationwide survey, the 5-year relative survival rates of NSCLC were 82% at stage I, 59% at stage II, 16% at stage III, and 10% at stage IV, and the 5-year relative survival rates of SCLC were 16% in cases with limited disease, and 4% in cases with extensive disease.


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