1.Cynaropicrin Induces Reactive Oxygen Species-Dependent Paraptosis-Like Cell Death in Human Liver Cancer Cells
Min Yeong KIM ; Hee-Jae CHA ; Su Hyun HONG ; Sung-Kwon MOON ; Taeg Kyu KWON ; Young-Chae CHANG ; Gi Young KIM ; Jin Won HYUN ; A-Young NAM ; Jung-Hyun SHIM ; Yung Hyun CHOI
Biomolecules & Therapeutics 2025;33(3):470-482
Cynaropicrin, a sesquiterpene lactone found in artichoke leaves exerts diverse pharmacological effects. This study investigated whether cynaropicrin has a paraptosis-like cell death effect in human hepatocellular carcinoma Hep3B cells in addition to the apoptotic effects reported in several cancer cell lines. Cynaropicrin-induced cytotoxicity and cytoplasmic vacuolation, a key characteristic of paraptosis, were not ameliorated by inhibitors of necroptosis, autophagy, or pan caspase inhibitors in Hep3B cells. Our study showed that cynaropicrin-induced cytotoxicity was accompanied by mitochondrial dysfunction and endoplasmic reticulum stress along with increased cellular calcium ion levels. These effects were significantly mitigated by endoplasmic reticulum stress inhibitor or protein synthesis inhibitor. Moreover, cynaropicrin treatment in Hep3B cells increased reactive oxygen species generation and downregulated apoptosis-linked gene 2-interacting protein X (Alix), a protein that inhibits paraptosis. The addition of the reactive oxygen species scavenger N-acetyl-L-cysteine (NAC) neutralized cynaropicrin-induced changes in Alix expression and endoplasmic reticulum stress marker proteins counteracting endoplasmic reticulum stress and mitochondrial impairment. This demonstrates a close relationship between endoplasmic reticulum stress and reactive oxygen species generation. Additionally, cynaropicrin activated p38 mitogen activated protein kinase and a selective p38 mitogen activated protein kinase blocker alleviated the biological phenomena induced by cynaropicrin. NAC pretreatment showed the best reversal of cynaropicrin induced vacuolation and cellular inactivity. Our findings suggest that cynaropicrin induced oxidative stress in Hep3B cells contributes to paraptotic events including endoplasmic reticulum stress and mitochondrial damage.
2.Proposal of age definition for early-onset gastric cancer based on the Korean Gastric Cancer Association nationwide survey data: a retrospective observational study
Seong-A JEONG ; Ji Sung LEE ; Ba Ool SEONG ; Seul-gi OH ; Chang Seok KO ; Sa-Hong MIN ; Chung Sik GONG ; Beom Su KIM ; Moon-Won YOO ; Jeong Hwan YOOK ; In-Seob LEE ;
Annals of Surgical Treatment and Research 2025;108(4):245-255
Purpose:
This study aimed to define an optimal age cutoff for early-onset gastric cancer (EOGC) and compare its characteristics with those of late-onset gastric cancer (LOGC) using nationwide survey data.
Methods:
Using data from a nationwide survey, this comprehensive population-based study analyzed data spanning 3 years (2009, 2014, and 2019). The joinpoint analysis and interrupted time series (ITS) methodology were employed to identify age cutoffs for EOGC based on the sex ratio and tumor histology. Clinicopathologic characteristics and surgical outcomes were compared between the EOGC and LOGC groups.
Results:
The age cutoff for defining EOGC was suggested to be 50 years, supported by joinpoint and ITS analyses. Early gastric cancer was predominantly present in the EOGC and LOGC groups. Patients with EOGC comprised 20.3% of the total study cohort and demonstrated a more advanced disease stage compared to patients with LOGC. However, patients with EOGC underwent more minimally invasive surgeries, experienced shorter hospital stays, and had lower postoperative morbidity and mortality rates.
Conclusion
This study proposes an age of ≤50 years as a criterion for defining EOGC and highlights its features compared to LOGC. Further research using this criterion should guide tailored treatment strategies and improve outcomes for young patients with gastric cancer.
3.Appropriateness of multidisciplinary treatment related to the adequacy evaluation of gastric cancer from the surgeon’s point of view: a retrospective cohort study
Ba Ool SEONG ; Seul-Gi OH ; Chang Seok KO ; Sa-Hong MIN ; Chung Sik GONG ; In-Seob LEE ; Beom Su KIM ; Jeong Hwan YOOK ; Moon-Won YOO
Annals of Surgical Treatment and Research 2025;108(4):240-244
Purpose:
Multidisciplinary treatment (MDT) in gastric cancer is an effective approach for establishing treatment plans.However, the appropriateness of using “ratio of MDT” as an item for evaluating the adequacy of gastric cancer treatment in Korea has not been previously researched. The purpose of this study is to verify whether the “ratio of MDT” is appropriate as an item for gastric cancer adequacy evaluation from the surgeon’s perspective.
Methods:
This study involved 142 patients who received MDT at our hospital between December 2015 and January 2023.Patients were divided into 2 groups based on the date when gastric cancer adequacy evaluation was implemented; there were 71 patients before and after the evaluation was conducted, respectively. Based on electronic medical records, the initial plan prepared before the MDT clinic and the final plan prepared after the clinic were compared to determine whether the plan was changed.
Results:
The average age of patients who received MDT before and after the evaluation was 64.8 and 62.2 years, respectively. Overall, 50 and 21 patients were male (70.4%) and female (29.6%), respectively, in both groups. Before the evaluation, 26 patients (36.6%) who received MDT changed their treatment plans after visiting the clinic, and 15 patients (21.1%) who received MDT after the evaluation had their treatment plans modified. Groups who received MDT and changes in treatment plans were significantly correlated (P = 0.042).
Conclusion
Our findings suggest that including the “ratio of MDT” as an item of gastric cancer adequacy evaluation needs reassessment.
4.CORRIGENDUM: Proposal of age definition for early-onset gastric cancer based on the Korean Gastric Cancer Association nationwide survey data: a retrospective observational study
Seong-A JEONG ; Ji Sung LEE ; Ba Ool SEONG ; Seul-gi OH ; Chang Seok KO ; Sa-Hong MIN ; Chung Sik GONG ; Beom Su KIM ; Moon-Won YOO ; Jeong Hwan YOOK ; In-Seob LEE ;
Annals of Surgical Treatment and Research 2025;108(5):331-331
5.Palliative Care and Hospice for Heart Failure Patients: Position Statement From the Korean Society of Heart Failure
Seung-Mok LEE ; Hae-Young LEE ; Shin Hye YOO ; Hyun-Jai CHO ; Jong-Chan YOUN ; Seong-Mi PARK ; Jin-Ok JEONG ; Min-Seok KIM ; Chi Young SHIM ; Jin Joo PARK ; Kye Hun KIM ; Eung Ju KIM ; Jeong Hoon YANG ; Jae Yeong CHO ; Sang-Ho JO ; Kyung-Kuk HWANG ; Ju-Hee LEE ; In-Cheol KIM ; Gi Beom KIM ; Jung Hyun CHOI ; Sung-Hee SHIN ; Wook-Jin CHUNG ; Seok-Min KANG ; Myeong Chan CHO ; Dae-Gyun PARK ; Byung-Su YOO
International Journal of Heart Failure 2025;7(1):32-46
Heart failure (HF) is a major cause of mortality and morbidity in South Korea, imposing substantial physical, emotional, and financial burdens on patients and society. Despite the high burden of symptom and complex care needs of HF patients, palliative care and hospice services remain underutilized in South Korea due to cultural, institutional, and knowledge-related barriers. This position statement from the Korean Society of Heart Failure emphasizes the need for integrating palliative and hospice care into HF management to improve quality of life and support holistic care for patients and their families. By clarifying the role of palliative care in HF and proposing practical referral criteria, this position statement aims to bridge the gap between HF and palliative care services in South Korea, ultimately improving patient-centered outcomes and aligning treatment with the goals and values of HF patients.
6.Proposal of age definition for early-onset gastric cancer based on the Korean Gastric Cancer Association nationwide survey data: a retrospective observational study
Seong-A JEONG ; Ji Sung LEE ; Ba Ool SEONG ; Seul-gi OH ; Chang Seok KO ; Sa-Hong MIN ; Chung Sik GONG ; Beom Su KIM ; Moon-Won YOO ; Jeong Hwan YOOK ; In-Seob LEE ;
Annals of Surgical Treatment and Research 2025;108(4):245-255
Purpose:
This study aimed to define an optimal age cutoff for early-onset gastric cancer (EOGC) and compare its characteristics with those of late-onset gastric cancer (LOGC) using nationwide survey data.
Methods:
Using data from a nationwide survey, this comprehensive population-based study analyzed data spanning 3 years (2009, 2014, and 2019). The joinpoint analysis and interrupted time series (ITS) methodology were employed to identify age cutoffs for EOGC based on the sex ratio and tumor histology. Clinicopathologic characteristics and surgical outcomes were compared between the EOGC and LOGC groups.
Results:
The age cutoff for defining EOGC was suggested to be 50 years, supported by joinpoint and ITS analyses. Early gastric cancer was predominantly present in the EOGC and LOGC groups. Patients with EOGC comprised 20.3% of the total study cohort and demonstrated a more advanced disease stage compared to patients with LOGC. However, patients with EOGC underwent more minimally invasive surgeries, experienced shorter hospital stays, and had lower postoperative morbidity and mortality rates.
Conclusion
This study proposes an age of ≤50 years as a criterion for defining EOGC and highlights its features compared to LOGC. Further research using this criterion should guide tailored treatment strategies and improve outcomes for young patients with gastric cancer.
7.Appropriateness of multidisciplinary treatment related to the adequacy evaluation of gastric cancer from the surgeon’s point of view: a retrospective cohort study
Ba Ool SEONG ; Seul-Gi OH ; Chang Seok KO ; Sa-Hong MIN ; Chung Sik GONG ; In-Seob LEE ; Beom Su KIM ; Jeong Hwan YOOK ; Moon-Won YOO
Annals of Surgical Treatment and Research 2025;108(4):240-244
Purpose:
Multidisciplinary treatment (MDT) in gastric cancer is an effective approach for establishing treatment plans.However, the appropriateness of using “ratio of MDT” as an item for evaluating the adequacy of gastric cancer treatment in Korea has not been previously researched. The purpose of this study is to verify whether the “ratio of MDT” is appropriate as an item for gastric cancer adequacy evaluation from the surgeon’s perspective.
Methods:
This study involved 142 patients who received MDT at our hospital between December 2015 and January 2023.Patients were divided into 2 groups based on the date when gastric cancer adequacy evaluation was implemented; there were 71 patients before and after the evaluation was conducted, respectively. Based on electronic medical records, the initial plan prepared before the MDT clinic and the final plan prepared after the clinic were compared to determine whether the plan was changed.
Results:
The average age of patients who received MDT before and after the evaluation was 64.8 and 62.2 years, respectively. Overall, 50 and 21 patients were male (70.4%) and female (29.6%), respectively, in both groups. Before the evaluation, 26 patients (36.6%) who received MDT changed their treatment plans after visiting the clinic, and 15 patients (21.1%) who received MDT after the evaluation had their treatment plans modified. Groups who received MDT and changes in treatment plans were significantly correlated (P = 0.042).
Conclusion
Our findings suggest that including the “ratio of MDT” as an item of gastric cancer adequacy evaluation needs reassessment.
8.CORRIGENDUM: Proposal of age definition for early-onset gastric cancer based on the Korean Gastric Cancer Association nationwide survey data: a retrospective observational study
Seong-A JEONG ; Ji Sung LEE ; Ba Ool SEONG ; Seul-gi OH ; Chang Seok KO ; Sa-Hong MIN ; Chung Sik GONG ; Beom Su KIM ; Moon-Won YOO ; Jeong Hwan YOOK ; In-Seob LEE ;
Annals of Surgical Treatment and Research 2025;108(5):331-331
9.Cynaropicrin Induces Reactive Oxygen Species-Dependent Paraptosis-Like Cell Death in Human Liver Cancer Cells
Min Yeong KIM ; Hee-Jae CHA ; Su Hyun HONG ; Sung-Kwon MOON ; Taeg Kyu KWON ; Young-Chae CHANG ; Gi Young KIM ; Jin Won HYUN ; A-Young NAM ; Jung-Hyun SHIM ; Yung Hyun CHOI
Biomolecules & Therapeutics 2025;33(3):470-482
Cynaropicrin, a sesquiterpene lactone found in artichoke leaves exerts diverse pharmacological effects. This study investigated whether cynaropicrin has a paraptosis-like cell death effect in human hepatocellular carcinoma Hep3B cells in addition to the apoptotic effects reported in several cancer cell lines. Cynaropicrin-induced cytotoxicity and cytoplasmic vacuolation, a key characteristic of paraptosis, were not ameliorated by inhibitors of necroptosis, autophagy, or pan caspase inhibitors in Hep3B cells. Our study showed that cynaropicrin-induced cytotoxicity was accompanied by mitochondrial dysfunction and endoplasmic reticulum stress along with increased cellular calcium ion levels. These effects were significantly mitigated by endoplasmic reticulum stress inhibitor or protein synthesis inhibitor. Moreover, cynaropicrin treatment in Hep3B cells increased reactive oxygen species generation and downregulated apoptosis-linked gene 2-interacting protein X (Alix), a protein that inhibits paraptosis. The addition of the reactive oxygen species scavenger N-acetyl-L-cysteine (NAC) neutralized cynaropicrin-induced changes in Alix expression and endoplasmic reticulum stress marker proteins counteracting endoplasmic reticulum stress and mitochondrial impairment. This demonstrates a close relationship between endoplasmic reticulum stress and reactive oxygen species generation. Additionally, cynaropicrin activated p38 mitogen activated protein kinase and a selective p38 mitogen activated protein kinase blocker alleviated the biological phenomena induced by cynaropicrin. NAC pretreatment showed the best reversal of cynaropicrin induced vacuolation and cellular inactivity. Our findings suggest that cynaropicrin induced oxidative stress in Hep3B cells contributes to paraptotic events including endoplasmic reticulum stress and mitochondrial damage.
10.Proposal of age definition for early-onset gastric cancer based on the Korean Gastric Cancer Association nationwide survey data: a retrospective observational study
Seong-A JEONG ; Ji Sung LEE ; Ba Ool SEONG ; Seul-gi OH ; Chang Seok KO ; Sa-Hong MIN ; Chung Sik GONG ; Beom Su KIM ; Moon-Won YOO ; Jeong Hwan YOOK ; In-Seob LEE ;
Annals of Surgical Treatment and Research 2025;108(4):245-255
Purpose:
This study aimed to define an optimal age cutoff for early-onset gastric cancer (EOGC) and compare its characteristics with those of late-onset gastric cancer (LOGC) using nationwide survey data.
Methods:
Using data from a nationwide survey, this comprehensive population-based study analyzed data spanning 3 years (2009, 2014, and 2019). The joinpoint analysis and interrupted time series (ITS) methodology were employed to identify age cutoffs for EOGC based on the sex ratio and tumor histology. Clinicopathologic characteristics and surgical outcomes were compared between the EOGC and LOGC groups.
Results:
The age cutoff for defining EOGC was suggested to be 50 years, supported by joinpoint and ITS analyses. Early gastric cancer was predominantly present in the EOGC and LOGC groups. Patients with EOGC comprised 20.3% of the total study cohort and demonstrated a more advanced disease stage compared to patients with LOGC. However, patients with EOGC underwent more minimally invasive surgeries, experienced shorter hospital stays, and had lower postoperative morbidity and mortality rates.
Conclusion
This study proposes an age of ≤50 years as a criterion for defining EOGC and highlights its features compared to LOGC. Further research using this criterion should guide tailored treatment strategies and improve outcomes for young patients with gastric cancer.

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