1.FDFT1 Acts as a Negative Regulator of Autophagy by Modulating AMPK–ULK1 Signaling in Hepatocellular Carcinoma Cells
Thi Ha NGUYEN ; Yongook LEE ; Minh Tuan NGUYEN ; Seoung Gyu CHOI ; Phuong Ngan NGUYEN ; Boram KIM ; Eun Ji KIM ; Gyeoung Jin KANG ; Mi Kyung PARK ; Sung Hoon LEE ; Sang Geon KIM ; Chang Hoon LEE
Biomolecules & Therapeutics 2026;34(3):632-640
Autophagy is a conserved catabolic process that degrades proteins and damaged organelles to maintain cellular homeostasis, and its role in cancer depends on stage and context. Farnesyl-diphosphate farnesyltransferase 1 (FDFT1) is an essential enzyme in the sterol branch of the mevalonate pathway, but its functions in hepatocellular carcinoma (HCC) and in the regulation of autophagy remain poorly understood. In this study, we show that FDFT1 acts as a negative regulator of autophagy in HCC cells. Loss of FDFT1 led to increased autophagosome formation and fusion with lysosomes, whereas its overexpression suppressed both basal and induced autophagy. These changes were associated with AMPK–ULK1 signaling, suggesting that FDFT1 influences a central pathway controlling autophagy. Our findings connect cholesterol metabolism with autophagy regulation and tumor growth, highlighting FDFT1 as a potential prognostic marker and therapeutic target in liver cancer.
2.Tumor-Associated Macrophage Infiltration and PD-L1 Expression in Gastric Cancer According to a Modified TCGA-Based Classification
Boram SONG ; Dong-Hoe KOO ; Eo Jin KIM ; In-Gu DO ; Jinah CHU ; Kyungeun KIM ; Hyebin LEE ; Min-Jung KWON ; Jung Ho PARK ; Byung Ho SON ; Chang Hak YOO ; Seoung Wan CHAE
Journal of Gastric Cancer 2026;26(2):247-259
Purpose:
Although gastric cancer (GC) exhibits significant genomic heterogeneity, the clinical implications of its immune microenvironment remain poorly understood.
Materials and Methods:
We retrospectively evaluated patients with GC who underwent gastrectomies between 2011 and 2014. The tumors were analyzed for Epstein–Barr virus (EBV), microsatellite instability-high (MSI-H), tumor-infiltrating lymphocytes (CD3), tumor-associated macrophages (CD68 and CD163), and programmed death-ligand 1 (PD-L1) expression. Tumors were classified using the modified The Cancer Genome Atlas scheme, and their clinical characteristics were compared.
Results:
A total of 567 patients were classified into EBV (6%), MSI-H (10%), chromosomal instability-like (36%), and genomically stable-like (48%) subtypes. EBV tumors exhibited the highest PD-L1 expression (85%) and immune infiltration by CD3+ T cells (86%), CD68+ macrophages (58%), and CD163+ macrophages (40%). High CD68+ macrophage tumors were associated with advanced stages and worse 5-year disease-free survival (83% vs. 95%; P<0.001);however, this association was not independently significant after adjusting for the tumor-nodemetastasis stage. PD-L1 expression did not significantly affect the survival outcomes.
Conclusions
GC subtypes have distinct immune microenvironments that influence prognosis. Our findings highlight the prognostic and therapeutic potential of immune profiling in GC.
3.Risk Factors of FEV 1 /FVC Decline in COPD Patients
Na Young KIM ; Deog Kyeom KIM ; Shinhee PARK ; Yong Il HWANG ; Hyewon SEO ; Dongil PARK ; Seoung Ju PARK ; Jin Hwa LEE ; Kwang Ha YOO ; Hyun Woo LEE
Journal of Korean Medical Science 2025;40(6):e32-
Background:
Factors influencing the decline in forced expiratory volume in one second (FEV1 )/forced vital capacity (FVC) for chronic obstructive pulmonary disease (COPD) progression remain uncertain. We aimed to identify risk factors associated with rapid FEV1 / FVC decline in patients with COPD.
Methods:
This multi-center observational study was conducted from January 2012 to December 2022. Eligible patients were monitored with symptoms, spirometric tests, and treatment patterns over 3 years. Rapid FEV1 /FVC decliners were defined as the quartile of patients exhibiting the highest annualized percentage decline in FEV1 /FVC.
Results:
Among 1,725 patients, 435 exhibited rapid FEV1 /FVC decline, with an annual change of −2.5%p (interquartile range, −3.5 to −2.0). Rapid FEV1 /FVC decliners exhibited lower body mass index (BMI), higher smoking rates, elevated post-bronchodilator (BD) FEV1 , higher post-BD FEV1 / FVC, and a lower prevalence of Staging of Airflow Obstruction by Ratio (STAR) stage IV. Rapid FEV1 /FVC decline was not linked to the annual exacerbation rate, but there was an association with symptom deterioration and FEV1 decline. In multivariable analyses, low BMI, current smoking, increased modified Medical Research Council dyspnoea score, low post-BD FEV1 , low STAR stage, high forced mid-expiratory flow (FEF 25-75% ), accelerated FEV1 decline, and not initiating dual BD therapy were identified as independent risk factors for rapid FEV1 /FVC decline.
Conclusion
We identified the risk factors for rapid FEV1 /FVC decline, including BMI, smoking, symptoms deterioration, FEV1 decline, and adherence to standard inhaler treatment. Our findings underscore the potential benefits of maintaining consistent use of long-acting beta-agonist/long-acting muscarinic antagonist even in the presence of worsening symptoms, in attenuating FEV1 /FVC decline.
4.Adherence to Pharmacological Management Guidelines for Stable Chronic Obstructive Lung Disease
Sang Min HAN ; Hyo Seon KIM ; Seung Yong PARK ; Heung Bum LEE ; Young Bum PARK ; Chin Kook RHEE ; Youlim KIM ; Seoung Ju PARK
Tuberculosis and Respiratory Diseases 2025;88(2):310-321
Background:
This study evaluated adherence to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) and Korean guidelines in the prescription patterns of respiratory specialists for stable chronic obstructive pulmonary disease (COPD) management.
Methods:
Data were collected on medications from 2011 to 2022 using the Korea COPD Subtype Study (KOCOSS) cohort. Patients were divided into two groups: those registered before and after 2019, and we analyzed the percentage of patients meeting the recommended treatment criteria established by each guideline.
Results:
Among 3,477 patients, 85.6% received pharmacological therapy, and 81.6% utilized inhaled medications. Compared to patients enrolled before 2019, there was an increase in inhaler prescriptions among those registered after 2019 (79.7% vs. 86.7%), with dual bronchodilators being the predominant therapy prescribed. Of the patients receiving treatment, 56.9% adhered to the Korean 2018 guideline. Compliance with the GOLD 2019 and GOLD 2023 guidelines was observed in 31.3% and 28.0% of cases, respectively. When analyzing inhaler prescription patterns according to both subgroups and considering the Korean 2018, GOLD 2019, and GOLD 2023 guidelines concurrently, the adherence rates were as follows: (56.6%, 37.8%, 24.0%) and (57.7%, 14.0%, 38.6%).
Conclusion
Adherence rates were higher for the Korean guideline compared to the GOLD recommendations. Furthermore, alignment with both the Korean 2018 and GOLD 2023 guidelines increased among patients enrolled after 2019, compared to those registered earlier. These findings suggest that physicians are modifying their therapeutic strategies to align with both domestic and recent international guidelines.
5.Risk Factors of FEV 1 /FVC Decline in COPD Patients
Na Young KIM ; Deog Kyeom KIM ; Shinhee PARK ; Yong Il HWANG ; Hyewon SEO ; Dongil PARK ; Seoung Ju PARK ; Jin Hwa LEE ; Kwang Ha YOO ; Hyun Woo LEE
Journal of Korean Medical Science 2025;40(6):e32-
Background:
Factors influencing the decline in forced expiratory volume in one second (FEV1 )/forced vital capacity (FVC) for chronic obstructive pulmonary disease (COPD) progression remain uncertain. We aimed to identify risk factors associated with rapid FEV1 / FVC decline in patients with COPD.
Methods:
This multi-center observational study was conducted from January 2012 to December 2022. Eligible patients were monitored with symptoms, spirometric tests, and treatment patterns over 3 years. Rapid FEV1 /FVC decliners were defined as the quartile of patients exhibiting the highest annualized percentage decline in FEV1 /FVC.
Results:
Among 1,725 patients, 435 exhibited rapid FEV1 /FVC decline, with an annual change of −2.5%p (interquartile range, −3.5 to −2.0). Rapid FEV1 /FVC decliners exhibited lower body mass index (BMI), higher smoking rates, elevated post-bronchodilator (BD) FEV1 , higher post-BD FEV1 / FVC, and a lower prevalence of Staging of Airflow Obstruction by Ratio (STAR) stage IV. Rapid FEV1 /FVC decline was not linked to the annual exacerbation rate, but there was an association with symptom deterioration and FEV1 decline. In multivariable analyses, low BMI, current smoking, increased modified Medical Research Council dyspnoea score, low post-BD FEV1 , low STAR stage, high forced mid-expiratory flow (FEF 25-75% ), accelerated FEV1 decline, and not initiating dual BD therapy were identified as independent risk factors for rapid FEV1 /FVC decline.
Conclusion
We identified the risk factors for rapid FEV1 /FVC decline, including BMI, smoking, symptoms deterioration, FEV1 decline, and adherence to standard inhaler treatment. Our findings underscore the potential benefits of maintaining consistent use of long-acting beta-agonist/long-acting muscarinic antagonist even in the presence of worsening symptoms, in attenuating FEV1 /FVC decline.
6.Adherence to Pharmacological Management Guidelines for Stable Chronic Obstructive Lung Disease
Sang Min HAN ; Hyo Seon KIM ; Seung Yong PARK ; Heung Bum LEE ; Young Bum PARK ; Chin Kook RHEE ; Youlim KIM ; Seoung Ju PARK
Tuberculosis and Respiratory Diseases 2025;88(2):310-321
Background:
This study evaluated adherence to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) and Korean guidelines in the prescription patterns of respiratory specialists for stable chronic obstructive pulmonary disease (COPD) management.
Methods:
Data were collected on medications from 2011 to 2022 using the Korea COPD Subtype Study (KOCOSS) cohort. Patients were divided into two groups: those registered before and after 2019, and we analyzed the percentage of patients meeting the recommended treatment criteria established by each guideline.
Results:
Among 3,477 patients, 85.6% received pharmacological therapy, and 81.6% utilized inhaled medications. Compared to patients enrolled before 2019, there was an increase in inhaler prescriptions among those registered after 2019 (79.7% vs. 86.7%), with dual bronchodilators being the predominant therapy prescribed. Of the patients receiving treatment, 56.9% adhered to the Korean 2018 guideline. Compliance with the GOLD 2019 and GOLD 2023 guidelines was observed in 31.3% and 28.0% of cases, respectively. When analyzing inhaler prescription patterns according to both subgroups and considering the Korean 2018, GOLD 2019, and GOLD 2023 guidelines concurrently, the adherence rates were as follows: (56.6%, 37.8%, 24.0%) and (57.7%, 14.0%, 38.6%).
Conclusion
Adherence rates were higher for the Korean guideline compared to the GOLD recommendations. Furthermore, alignment with both the Korean 2018 and GOLD 2023 guidelines increased among patients enrolled after 2019, compared to those registered earlier. These findings suggest that physicians are modifying their therapeutic strategies to align with both domestic and recent international guidelines.
7.Risk Factors of FEV 1 /FVC Decline in COPD Patients
Na Young KIM ; Deog Kyeom KIM ; Shinhee PARK ; Yong Il HWANG ; Hyewon SEO ; Dongil PARK ; Seoung Ju PARK ; Jin Hwa LEE ; Kwang Ha YOO ; Hyun Woo LEE
Journal of Korean Medical Science 2025;40(6):e32-
Background:
Factors influencing the decline in forced expiratory volume in one second (FEV1 )/forced vital capacity (FVC) for chronic obstructive pulmonary disease (COPD) progression remain uncertain. We aimed to identify risk factors associated with rapid FEV1 / FVC decline in patients with COPD.
Methods:
This multi-center observational study was conducted from January 2012 to December 2022. Eligible patients were monitored with symptoms, spirometric tests, and treatment patterns over 3 years. Rapid FEV1 /FVC decliners were defined as the quartile of patients exhibiting the highest annualized percentage decline in FEV1 /FVC.
Results:
Among 1,725 patients, 435 exhibited rapid FEV1 /FVC decline, with an annual change of −2.5%p (interquartile range, −3.5 to −2.0). Rapid FEV1 /FVC decliners exhibited lower body mass index (BMI), higher smoking rates, elevated post-bronchodilator (BD) FEV1 , higher post-BD FEV1 / FVC, and a lower prevalence of Staging of Airflow Obstruction by Ratio (STAR) stage IV. Rapid FEV1 /FVC decline was not linked to the annual exacerbation rate, but there was an association with symptom deterioration and FEV1 decline. In multivariable analyses, low BMI, current smoking, increased modified Medical Research Council dyspnoea score, low post-BD FEV1 , low STAR stage, high forced mid-expiratory flow (FEF 25-75% ), accelerated FEV1 decline, and not initiating dual BD therapy were identified as independent risk factors for rapid FEV1 /FVC decline.
Conclusion
We identified the risk factors for rapid FEV1 /FVC decline, including BMI, smoking, symptoms deterioration, FEV1 decline, and adherence to standard inhaler treatment. Our findings underscore the potential benefits of maintaining consistent use of long-acting beta-agonist/long-acting muscarinic antagonist even in the presence of worsening symptoms, in attenuating FEV1 /FVC decline.
8.Risk Factors of FEV 1 /FVC Decline in COPD Patients
Na Young KIM ; Deog Kyeom KIM ; Shinhee PARK ; Yong Il HWANG ; Hyewon SEO ; Dongil PARK ; Seoung Ju PARK ; Jin Hwa LEE ; Kwang Ha YOO ; Hyun Woo LEE
Journal of Korean Medical Science 2025;40(6):e32-
Background:
Factors influencing the decline in forced expiratory volume in one second (FEV1 )/forced vital capacity (FVC) for chronic obstructive pulmonary disease (COPD) progression remain uncertain. We aimed to identify risk factors associated with rapid FEV1 / FVC decline in patients with COPD.
Methods:
This multi-center observational study was conducted from January 2012 to December 2022. Eligible patients were monitored with symptoms, spirometric tests, and treatment patterns over 3 years. Rapid FEV1 /FVC decliners were defined as the quartile of patients exhibiting the highest annualized percentage decline in FEV1 /FVC.
Results:
Among 1,725 patients, 435 exhibited rapid FEV1 /FVC decline, with an annual change of −2.5%p (interquartile range, −3.5 to −2.0). Rapid FEV1 /FVC decliners exhibited lower body mass index (BMI), higher smoking rates, elevated post-bronchodilator (BD) FEV1 , higher post-BD FEV1 / FVC, and a lower prevalence of Staging of Airflow Obstruction by Ratio (STAR) stage IV. Rapid FEV1 /FVC decline was not linked to the annual exacerbation rate, but there was an association with symptom deterioration and FEV1 decline. In multivariable analyses, low BMI, current smoking, increased modified Medical Research Council dyspnoea score, low post-BD FEV1 , low STAR stage, high forced mid-expiratory flow (FEF 25-75% ), accelerated FEV1 decline, and not initiating dual BD therapy were identified as independent risk factors for rapid FEV1 /FVC decline.
Conclusion
We identified the risk factors for rapid FEV1 /FVC decline, including BMI, smoking, symptoms deterioration, FEV1 decline, and adherence to standard inhaler treatment. Our findings underscore the potential benefits of maintaining consistent use of long-acting beta-agonist/long-acting muscarinic antagonist even in the presence of worsening symptoms, in attenuating FEV1 /FVC decline.
9.Adherence to Pharmacological Management Guidelines for Stable Chronic Obstructive Lung Disease
Sang Min HAN ; Hyo Seon KIM ; Seung Yong PARK ; Heung Bum LEE ; Young Bum PARK ; Chin Kook RHEE ; Youlim KIM ; Seoung Ju PARK
Tuberculosis and Respiratory Diseases 2025;88(2):310-321
Background:
This study evaluated adherence to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) and Korean guidelines in the prescription patterns of respiratory specialists for stable chronic obstructive pulmonary disease (COPD) management.
Methods:
Data were collected on medications from 2011 to 2022 using the Korea COPD Subtype Study (KOCOSS) cohort. Patients were divided into two groups: those registered before and after 2019, and we analyzed the percentage of patients meeting the recommended treatment criteria established by each guideline.
Results:
Among 3,477 patients, 85.6% received pharmacological therapy, and 81.6% utilized inhaled medications. Compared to patients enrolled before 2019, there was an increase in inhaler prescriptions among those registered after 2019 (79.7% vs. 86.7%), with dual bronchodilators being the predominant therapy prescribed. Of the patients receiving treatment, 56.9% adhered to the Korean 2018 guideline. Compliance with the GOLD 2019 and GOLD 2023 guidelines was observed in 31.3% and 28.0% of cases, respectively. When analyzing inhaler prescription patterns according to both subgroups and considering the Korean 2018, GOLD 2019, and GOLD 2023 guidelines concurrently, the adherence rates were as follows: (56.6%, 37.8%, 24.0%) and (57.7%, 14.0%, 38.6%).
Conclusion
Adherence rates were higher for the Korean guideline compared to the GOLD recommendations. Furthermore, alignment with both the Korean 2018 and GOLD 2023 guidelines increased among patients enrolled after 2019, compared to those registered earlier. These findings suggest that physicians are modifying their therapeutic strategies to align with both domestic and recent international guidelines.
10.Adherence to Pharmacological Management Guidelines for Stable Chronic Obstructive Lung Disease
Sang Min HAN ; Hyo Seon KIM ; Seung Yong PARK ; Heung Bum LEE ; Young Bum PARK ; Chin Kook RHEE ; Youlim KIM ; Seoung Ju PARK
Tuberculosis and Respiratory Diseases 2025;88(2):310-321
Background:
This study evaluated adherence to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) and Korean guidelines in the prescription patterns of respiratory specialists for stable chronic obstructive pulmonary disease (COPD) management.
Methods:
Data were collected on medications from 2011 to 2022 using the Korea COPD Subtype Study (KOCOSS) cohort. Patients were divided into two groups: those registered before and after 2019, and we analyzed the percentage of patients meeting the recommended treatment criteria established by each guideline.
Results:
Among 3,477 patients, 85.6% received pharmacological therapy, and 81.6% utilized inhaled medications. Compared to patients enrolled before 2019, there was an increase in inhaler prescriptions among those registered after 2019 (79.7% vs. 86.7%), with dual bronchodilators being the predominant therapy prescribed. Of the patients receiving treatment, 56.9% adhered to the Korean 2018 guideline. Compliance with the GOLD 2019 and GOLD 2023 guidelines was observed in 31.3% and 28.0% of cases, respectively. When analyzing inhaler prescription patterns according to both subgroups and considering the Korean 2018, GOLD 2019, and GOLD 2023 guidelines concurrently, the adherence rates were as follows: (56.6%, 37.8%, 24.0%) and (57.7%, 14.0%, 38.6%).
Conclusion
Adherence rates were higher for the Korean guideline compared to the GOLD recommendations. Furthermore, alignment with both the Korean 2018 and GOLD 2023 guidelines increased among patients enrolled after 2019, compared to those registered earlier. These findings suggest that physicians are modifying their therapeutic strategies to align with both domestic and recent international guidelines.

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