1.Licochalcone D Exerts Antitumor Activity in Human Colorectal Cancer Cells by Inducing ROS Generation and Phosphorylating JNK and p38 MAPK
Seung-On LEE ; Sang Hoon JOO ; Seung-Sik CHO ; Goo YOON ; Yung Hyun CHOI ; Jin Woo PARK ; Kwon-Yeon WEON ; Jung-Hyun SHIM
Biomolecules & Therapeutics 2025;33(2):344-354
		                        		
		                        			
		                        			 Anticancer activities of Licochalcone D (LCD) in human colorectal cancer (CRC) cells HCT116 and oxaliplatin-resistant HCT116 (HCT116-OxR) were determined. Cell viability assay and soft agar assay were used to analyze antiproliferative activity of LCD.Flow cytometry was performed to determine effects of LCD on apoptosis, cell cycle distribution, reactive oxygen species (ROS), mitochondrial membrane potential (MMP) dysfunction, and multi-caspase activity in CRC cells. Western blot analysis was used to monitor levels of proteins involved in cell cycle and apoptosis signaling pathways. LCD suppressed the growth and anchorageindependent colony formation of both HCT116 and HCT116-OxR cells. Cell cycle analysis by flow cytometry indicated that LCD induced cell cycle arrest and increased cells in sub-G1 phase. In parallel with the antiproliferative effect of LCD, LCD up-regulated levels of p21 and p27 while downregulating cyclin B1 and cdc2. In addition, phosphorylation levels of JNK and p38 mitogen-activated protein kinase (MAPK) were increased by LCD. Inhibition of these kinases somehow prevented the antiproliferative effect of LCD. Moreover, LCD increased ROS and deregulated mitochondrial membrane potential, leading to the activation of multiple caspases. An ROS scavenger N-acetyl-cysteine (NAC) or pan-caspase inhibitor Z-VAD-FMK prevented the antiproliferative effect of LCD, supporting that ROS generation and caspase activation mediated LCD-induced apoptosis in CRC cells. In conclusion, LCD exerted antitumor activity in CRC cells by inducing ROS generation and phosphorylation of JNK and p38 MAPK. These results support that LCD could be further developed as a chemotherapeutic agent for treating CRC. 
		                        		
		                        		
		                        		
		                        	
2.Licochalcone D Exerts Antitumor Activity in Human Colorectal Cancer Cells by Inducing ROS Generation and Phosphorylating JNK and p38 MAPK
Seung-On LEE ; Sang Hoon JOO ; Seung-Sik CHO ; Goo YOON ; Yung Hyun CHOI ; Jin Woo PARK ; Kwon-Yeon WEON ; Jung-Hyun SHIM
Biomolecules & Therapeutics 2025;33(2):344-354
		                        		
		                        			
		                        			 Anticancer activities of Licochalcone D (LCD) in human colorectal cancer (CRC) cells HCT116 and oxaliplatin-resistant HCT116 (HCT116-OxR) were determined. Cell viability assay and soft agar assay were used to analyze antiproliferative activity of LCD.Flow cytometry was performed to determine effects of LCD on apoptosis, cell cycle distribution, reactive oxygen species (ROS), mitochondrial membrane potential (MMP) dysfunction, and multi-caspase activity in CRC cells. Western blot analysis was used to monitor levels of proteins involved in cell cycle and apoptosis signaling pathways. LCD suppressed the growth and anchorageindependent colony formation of both HCT116 and HCT116-OxR cells. Cell cycle analysis by flow cytometry indicated that LCD induced cell cycle arrest and increased cells in sub-G1 phase. In parallel with the antiproliferative effect of LCD, LCD up-regulated levels of p21 and p27 while downregulating cyclin B1 and cdc2. In addition, phosphorylation levels of JNK and p38 mitogen-activated protein kinase (MAPK) were increased by LCD. Inhibition of these kinases somehow prevented the antiproliferative effect of LCD. Moreover, LCD increased ROS and deregulated mitochondrial membrane potential, leading to the activation of multiple caspases. An ROS scavenger N-acetyl-cysteine (NAC) or pan-caspase inhibitor Z-VAD-FMK prevented the antiproliferative effect of LCD, supporting that ROS generation and caspase activation mediated LCD-induced apoptosis in CRC cells. In conclusion, LCD exerted antitumor activity in CRC cells by inducing ROS generation and phosphorylation of JNK and p38 MAPK. These results support that LCD could be further developed as a chemotherapeutic agent for treating CRC. 
		                        		
		                        		
		                        		
		                        	
3.Licochalcone D Exerts Antitumor Activity in Human Colorectal Cancer Cells by Inducing ROS Generation and Phosphorylating JNK and p38 MAPK
Seung-On LEE ; Sang Hoon JOO ; Seung-Sik CHO ; Goo YOON ; Yung Hyun CHOI ; Jin Woo PARK ; Kwon-Yeon WEON ; Jung-Hyun SHIM
Biomolecules & Therapeutics 2025;33(2):344-354
		                        		
		                        			
		                        			 Anticancer activities of Licochalcone D (LCD) in human colorectal cancer (CRC) cells HCT116 and oxaliplatin-resistant HCT116 (HCT116-OxR) were determined. Cell viability assay and soft agar assay were used to analyze antiproliferative activity of LCD.Flow cytometry was performed to determine effects of LCD on apoptosis, cell cycle distribution, reactive oxygen species (ROS), mitochondrial membrane potential (MMP) dysfunction, and multi-caspase activity in CRC cells. Western blot analysis was used to monitor levels of proteins involved in cell cycle and apoptosis signaling pathways. LCD suppressed the growth and anchorageindependent colony formation of both HCT116 and HCT116-OxR cells. Cell cycle analysis by flow cytometry indicated that LCD induced cell cycle arrest and increased cells in sub-G1 phase. In parallel with the antiproliferative effect of LCD, LCD up-regulated levels of p21 and p27 while downregulating cyclin B1 and cdc2. In addition, phosphorylation levels of JNK and p38 mitogen-activated protein kinase (MAPK) were increased by LCD. Inhibition of these kinases somehow prevented the antiproliferative effect of LCD. Moreover, LCD increased ROS and deregulated mitochondrial membrane potential, leading to the activation of multiple caspases. An ROS scavenger N-acetyl-cysteine (NAC) or pan-caspase inhibitor Z-VAD-FMK prevented the antiproliferative effect of LCD, supporting that ROS generation and caspase activation mediated LCD-induced apoptosis in CRC cells. In conclusion, LCD exerted antitumor activity in CRC cells by inducing ROS generation and phosphorylation of JNK and p38 MAPK. These results support that LCD could be further developed as a chemotherapeutic agent for treating CRC. 
		                        		
		                        		
		                        		
		                        	
4.Characteristics of High-Risk Groups for Suicide in Korea Before and After the COVID-19 Pandemic: K-COMPASS Cohort Study
Jeong Hun YANG ; Dae Hun KANG ; C. Hyung Keun PARK ; Min Ji KIM ; Sang Jin RHEE ; Min-Hyuk KIM ; Jinhee LEE ; Sang Yeol LEE ; Won Sub KANG ; Seong-Jin CHO ; Shin Gyeom KIM ; Se-Hoon SHIM ; Jung-Joon MOON ; Jieun YOO ; Weon-Young LEE ; Yong Min AHN
Journal of Korean Neuropsychiatric Association 2024;63(4):246-259
		                        		
		                        			 Objectives:
		                        			This study examined the changes in the characteristics of high-risk suicide groups in South Korea before and after the COVID-19 pandemic using the Korean Cohort for the Model Predicting a Suicide and Suicide-related Behavior (K-COMPASS) cohort. 
		                        		
		                        			Methods:
		                        			The K-COMPASS is a longitudinal cohort study that started in 2015. The participants included suicide attempters and individuals with suicidal ideation from various hospitals and mental health centers in South Korea. This study compared the sociodemographic and psychiatric characteristics of 800 participants from the first cohort (2015–2019) with 511 participants from the second and third cohorts (2019–2024). Data were collected through structured interviews and validated scales. 
		                        		
		                        			Results:
		                        			The second and third cohort participants were younger, had a higher proportion of females, and exhibited more severe psychiatric symptoms and higher suicidal risk than the first cohort. The prevalence of physical illnesses decreased, while the use of psychiatric medications and the severity of mental health issues increased. In addition, significant sociodemographic changes were observed, such as higher educational levels and urban residency. 
		                        		
		                        			Conclusion
		                        			Significant shifts in the characteristics of high-risk suicide groups were observed during the COVID-19 pandemic, highlighting the need for targeted mental health interventions focusing on younger individuals and females to prevent suicide in high-risk groups. 
		                        		
		                        		
		                        		
		                        	
5.Characteristics of High-Risk Groups for Suicide in Korea Before and After the COVID-19 Pandemic: K-COMPASS Cohort Study
Jeong Hun YANG ; Dae Hun KANG ; C. Hyung Keun PARK ; Min Ji KIM ; Sang Jin RHEE ; Min-Hyuk KIM ; Jinhee LEE ; Sang Yeol LEE ; Won Sub KANG ; Seong-Jin CHO ; Shin Gyeom KIM ; Se-Hoon SHIM ; Jung-Joon MOON ; Jieun YOO ; Weon-Young LEE ; Yong Min AHN
Journal of Korean Neuropsychiatric Association 2024;63(4):246-259
		                        		
		                        			 Objectives:
		                        			This study examined the changes in the characteristics of high-risk suicide groups in South Korea before and after the COVID-19 pandemic using the Korean Cohort for the Model Predicting a Suicide and Suicide-related Behavior (K-COMPASS) cohort. 
		                        		
		                        			Methods:
		                        			The K-COMPASS is a longitudinal cohort study that started in 2015. The participants included suicide attempters and individuals with suicidal ideation from various hospitals and mental health centers in South Korea. This study compared the sociodemographic and psychiatric characteristics of 800 participants from the first cohort (2015–2019) with 511 participants from the second and third cohorts (2019–2024). Data were collected through structured interviews and validated scales. 
		                        		
		                        			Results:
		                        			The second and third cohort participants were younger, had a higher proportion of females, and exhibited more severe psychiatric symptoms and higher suicidal risk than the first cohort. The prevalence of physical illnesses decreased, while the use of psychiatric medications and the severity of mental health issues increased. In addition, significant sociodemographic changes were observed, such as higher educational levels and urban residency. 
		                        		
		                        			Conclusion
		                        			Significant shifts in the characteristics of high-risk suicide groups were observed during the COVID-19 pandemic, highlighting the need for targeted mental health interventions focusing on younger individuals and females to prevent suicide in high-risk groups. 
		                        		
		                        		
		                        		
		                        	
6.Chemotherapy response score no longer predicts survival outcomes in high-grade serous ovarian cancer patients with BRCA mutation and/or maintenance therapy
Young Joo LEE ; Yoon Kyung SHIN ; Nae Ry KIM ; Se Ik KIM ; Yoo-Young LEE ; Jeong-Yeol PARK ; Jae-Weon KIM ; Hyun-Woong CHO ; Jung-Yun LEE
Journal of Gynecologic Oncology 2024;35(6):e73-
		                        		
		                        			 Objective:
		                        			We aimed to revalidate the chemotherapy response score (CRS) system as a prognostic factor for ovarian cancer patients with breast cancer gene (BRCA) mutations or those receiving frontline poly-ADP ribose polymerase (PARP) inhibitors or bevacizumab as maintenance therapy. 
		                        		
		                        			Methods:
		                        			A retrospective analysis was performed using medical records of patients with high-grade serous carcinoma who received neoadjuvant chemotherapy followed by interval debulking surgery between January 2007 and December 2021 at 5 tertiary medical institutions in South Korea. At each hospital, pathologists independently assessed each slide of omental tissues obtained from surgery using the CRS system. Progression-free survival (PFS) and overall survival (OS) values were obtained using Kaplan-Meier analysis to evaluate the effect of BRCA mutation, maintenance therapy, and CRS on survival time. 
		                        		
		                        			Results:
		                        			Of 466 patients, BRCA mutations were detected in 156 (33.5%) and 131 (28.1%) were treated with maintenance therapy; 98 (21.0%) and 42 (9.0%) were treated with PARP inhibitors or bevacizumab, respectively. Patients with CRS3 had significantly longer PFS than those with CRS1 or 2 (24.7 vs. 16.8 months, p<0.001). However, there was no significant difference in PFS improvement between CRS3 patients and those with CRS1 or 2 with BRCA mutation (22.0 vs. 19.3 months, p=0.193). Moreover, no significant PFS prolongation was observed in CRS3 patients compared to CRS1 or 2 patients treated with PARP inhibitors or bevacizumab (24.3 vs. 22.4 months, p=0.851; 27.5 vs. 15.7 months, p=0.347, respectively). 
		                        		
		                        			Conclusion
		                        			CRS may not be a prognostic factor in patients with BRCA mutations and those receiving frontline maintenance therapy. 
		                        		
		                        		
		                        		
		                        	
7.Therapeutic effects of surgical debulking of metastatic lymph nodes in cervical cancer IIICr: a trial protocol for a phase III, multicenter, randomized controlled study (KGOG1047/DEBULK trial)
Bo Seong YUN ; Kwang-Beom LEE ; Keun Ho LEE ; Ha Kyun CHANG ; Joo-Young KIM ; Myong Cheol LIM ; Chel Hun CHOI ; Hanbyoul CHO ; Dae-Yeon KIM ; Yun Hwan KIM ; Joong Sub CHOI ; Chae Hyeong LEE ; Jae-Weon KIM ; Sang Wun KIM ; Yong Bae KIM ; Chi-Heum CHO ; Dae Gy HONG ; Yong Jung SONG ; Seob JEON ; Min Kyu KIM ; Dae Hoon JEONG ; Hyun PARK ; Seok Mo KIM ; Sang-Il PARK ; Jae-Yun SONG ; Asima MUKHOPADHYAY ; Dang Huy Quoc THINH ; Nirmala Chandralega KAMPAN ; Grace J. LEE ; Jae-Hoon KIM ; Keun-Yong EOM ; Ju-Won ROH
Journal of Gynecologic Oncology 2024;35(5):e57-
		                        		
		                        			 Background:
		                        			Bulky or multiple lymph node (LN) metastases are associated with poor prognosis in cervical cancer, and the size or number of LN metastases is not yet reflected in the staging system and therapeutic strategy. Although the therapeutic effects of surgical resection of bulky LNs before standard treatment have been reported in several retrospective studies, wellplanned randomized clinical studies are lacking. Therefore, the aim of the Korean Gynecologic Oncology Group (KGOG) 1047/DEBULK trial is to investigate whether the debulking surgery of bulky or multiple LNs prior to concurrent chemoradiation therapy (CCRT) improves the survival rate of patients with cervical cancer IIICr diagnosed by imaging tests. 
		                        		
		                        			Methods
		                        			The KGOG 1047/DEBULK trial is a phase III, multicenter, randomized clinical trial involving patients with bulky or multiple LN metastases in cervical cancer IIICr. This study will include patients with a short-axis diameter of a pelvic or para-aortic LN ≥2 cm or ≥3 LNs with a short-axis diameter ≥1 cm and for whom CCRT is planned. The treatment arms will be randomly allocated in a 1:1 ratio to either receive CCRT (control arm) or undergo surgical debulking of bulky or multiple LNs before CCRT (experimental arm). CCRT consists of extended-field external beam radiotherapy/pelvic radiotherapy, brachytherapy and LN boost, and weekly chemotherapy with cisplatin (40 mg/m 2 ), 4–6 times administered intravenously.The primary endpoint will be 3-year progression-free survival rate. The secondary endpoints will be 3-year overall survival rate, treatment-related complications, and accuracy of radiological diagnosis of bulky or multiple LNs. 
		                        		
		                        		
		                        		
		                        	
8.Chemotherapy response score no longer predicts survival outcomes in high-grade serous ovarian cancer patients with BRCA mutation and/or maintenance therapy
Young Joo LEE ; Yoon Kyung SHIN ; Nae Ry KIM ; Se Ik KIM ; Yoo-Young LEE ; Jeong-Yeol PARK ; Jae-Weon KIM ; Hyun-Woong CHO ; Jung-Yun LEE
Journal of Gynecologic Oncology 2024;35(6):e73-
		                        		
		                        			 Objective:
		                        			We aimed to revalidate the chemotherapy response score (CRS) system as a prognostic factor for ovarian cancer patients with breast cancer gene (BRCA) mutations or those receiving frontline poly-ADP ribose polymerase (PARP) inhibitors or bevacizumab as maintenance therapy. 
		                        		
		                        			Methods:
		                        			A retrospective analysis was performed using medical records of patients with high-grade serous carcinoma who received neoadjuvant chemotherapy followed by interval debulking surgery between January 2007 and December 2021 at 5 tertiary medical institutions in South Korea. At each hospital, pathologists independently assessed each slide of omental tissues obtained from surgery using the CRS system. Progression-free survival (PFS) and overall survival (OS) values were obtained using Kaplan-Meier analysis to evaluate the effect of BRCA mutation, maintenance therapy, and CRS on survival time. 
		                        		
		                        			Results:
		                        			Of 466 patients, BRCA mutations were detected in 156 (33.5%) and 131 (28.1%) were treated with maintenance therapy; 98 (21.0%) and 42 (9.0%) were treated with PARP inhibitors or bevacizumab, respectively. Patients with CRS3 had significantly longer PFS than those with CRS1 or 2 (24.7 vs. 16.8 months, p<0.001). However, there was no significant difference in PFS improvement between CRS3 patients and those with CRS1 or 2 with BRCA mutation (22.0 vs. 19.3 months, p=0.193). Moreover, no significant PFS prolongation was observed in CRS3 patients compared to CRS1 or 2 patients treated with PARP inhibitors or bevacizumab (24.3 vs. 22.4 months, p=0.851; 27.5 vs. 15.7 months, p=0.347, respectively). 
		                        		
		                        			Conclusion
		                        			CRS may not be a prognostic factor in patients with BRCA mutations and those receiving frontline maintenance therapy. 
		                        		
		                        		
		                        		
		                        	
9.Therapeutic effects of surgical debulking of metastatic lymph nodes in cervical cancer IIICr: a trial protocol for a phase III, multicenter, randomized controlled study (KGOG1047/DEBULK trial)
Bo Seong YUN ; Kwang-Beom LEE ; Keun Ho LEE ; Ha Kyun CHANG ; Joo-Young KIM ; Myong Cheol LIM ; Chel Hun CHOI ; Hanbyoul CHO ; Dae-Yeon KIM ; Yun Hwan KIM ; Joong Sub CHOI ; Chae Hyeong LEE ; Jae-Weon KIM ; Sang Wun KIM ; Yong Bae KIM ; Chi-Heum CHO ; Dae Gy HONG ; Yong Jung SONG ; Seob JEON ; Min Kyu KIM ; Dae Hoon JEONG ; Hyun PARK ; Seok Mo KIM ; Sang-Il PARK ; Jae-Yun SONG ; Asima MUKHOPADHYAY ; Dang Huy Quoc THINH ; Nirmala Chandralega KAMPAN ; Grace J. LEE ; Jae-Hoon KIM ; Keun-Yong EOM ; Ju-Won ROH
Journal of Gynecologic Oncology 2024;35(5):e57-
		                        		
		                        			 Background:
		                        			Bulky or multiple lymph node (LN) metastases are associated with poor prognosis in cervical cancer, and the size or number of LN metastases is not yet reflected in the staging system and therapeutic strategy. Although the therapeutic effects of surgical resection of bulky LNs before standard treatment have been reported in several retrospective studies, wellplanned randomized clinical studies are lacking. Therefore, the aim of the Korean Gynecologic Oncology Group (KGOG) 1047/DEBULK trial is to investigate whether the debulking surgery of bulky or multiple LNs prior to concurrent chemoradiation therapy (CCRT) improves the survival rate of patients with cervical cancer IIICr diagnosed by imaging tests. 
		                        		
		                        			Methods
		                        			The KGOG 1047/DEBULK trial is a phase III, multicenter, randomized clinical trial involving patients with bulky or multiple LN metastases in cervical cancer IIICr. This study will include patients with a short-axis diameter of a pelvic or para-aortic LN ≥2 cm or ≥3 LNs with a short-axis diameter ≥1 cm and for whom CCRT is planned. The treatment arms will be randomly allocated in a 1:1 ratio to either receive CCRT (control arm) or undergo surgical debulking of bulky or multiple LNs before CCRT (experimental arm). CCRT consists of extended-field external beam radiotherapy/pelvic radiotherapy, brachytherapy and LN boost, and weekly chemotherapy with cisplatin (40 mg/m 2 ), 4–6 times administered intravenously.The primary endpoint will be 3-year progression-free survival rate. The secondary endpoints will be 3-year overall survival rate, treatment-related complications, and accuracy of radiological diagnosis of bulky or multiple LNs. 
		                        		
		                        		
		                        		
		                        	
10.Characteristics of High-Risk Groups for Suicide in Korea Before and After the COVID-19 Pandemic: K-COMPASS Cohort Study
Jeong Hun YANG ; Dae Hun KANG ; C. Hyung Keun PARK ; Min Ji KIM ; Sang Jin RHEE ; Min-Hyuk KIM ; Jinhee LEE ; Sang Yeol LEE ; Won Sub KANG ; Seong-Jin CHO ; Shin Gyeom KIM ; Se-Hoon SHIM ; Jung-Joon MOON ; Jieun YOO ; Weon-Young LEE ; Yong Min AHN
Journal of Korean Neuropsychiatric Association 2024;63(4):246-259
		                        		
		                        			 Objectives:
		                        			This study examined the changes in the characteristics of high-risk suicide groups in South Korea before and after the COVID-19 pandemic using the Korean Cohort for the Model Predicting a Suicide and Suicide-related Behavior (K-COMPASS) cohort. 
		                        		
		                        			Methods:
		                        			The K-COMPASS is a longitudinal cohort study that started in 2015. The participants included suicide attempters and individuals with suicidal ideation from various hospitals and mental health centers in South Korea. This study compared the sociodemographic and psychiatric characteristics of 800 participants from the first cohort (2015–2019) with 511 participants from the second and third cohorts (2019–2024). Data were collected through structured interviews and validated scales. 
		                        		
		                        			Results:
		                        			The second and third cohort participants were younger, had a higher proportion of females, and exhibited more severe psychiatric symptoms and higher suicidal risk than the first cohort. The prevalence of physical illnesses decreased, while the use of psychiatric medications and the severity of mental health issues increased. In addition, significant sociodemographic changes were observed, such as higher educational levels and urban residency. 
		                        		
		                        			Conclusion
		                        			Significant shifts in the characteristics of high-risk suicide groups were observed during the COVID-19 pandemic, highlighting the need for targeted mental health interventions focusing on younger individuals and females to prevent suicide in high-risk groups. 
		                        		
		                        		
		                        		
		                        	
            
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