1.Synergistic anticancer effects of mitochondria-targeting peptide combined with paclitaxel in breast cancer cells: a preclinical study
Juneyoung AHN ; Ok-Hee KIM ; Seongeon JIN ; Ja-Hyoung RYU ; Dosang LEE ; Woo-Chan PARK ; Say-June KIM
Annals of Surgical Treatment and Research 2025;108(2):108-123
Purpose:
Mitochondria-accumulating amphiphilic peptide (Mito-FF) was designed to selectively target mitochondria in cancer cells and enhance anticancer effects through its unique structure. Mito-FF consists of (1) diphenylalanine, a β-sheet-forming building block critical for self-assembly; (2) triphenylphosphonium, a mitochondrial targeting moiety guiding the peptide to mitochondria; and (3) pyrene, a fluorescent probe enabling visualization of its accumulation and selfassembly. This study evaluates the anticancer efficacy of Mito-FF in breast cancer cells and explores its combination with paclitaxel, a standard therapy for breast cancer, focusing on its modulation of the epithelial-mesenchymal transition (EMT) pathway.
Methods:
In vitro and in vivo experiments were performed using MCF-7 and MDA-MB-231 breast cancer cell lines and their respective xenograft models. Cell viability, migration, EMT marker expression, and apoptosis-related proteins were analyzed.
Results:
Mito-FF demonstrated superior inhibition of cell viability and migration compared to paclitaxel alone in both cell lines. Combination therapy with Mito-FF and paclitaxel resulted in enhanced reduction of cell viability and migration. EMT markers were significantly modulated, with decreased mesenchymal markers (Snail and vimentin) and increased epithelial marker (E-cadherin) following combination treatment. Furthermore, the combination therapy synergistically elevated proapoptotic markers such as poly (adenosine diphosphate-ribose) polymerase and reduced anti-apoptotic markers such as myeloid cell leukemia 1. In vivo experiments revealed a marked reduction in tumor volume with combination therapy, accompanied by the highest expression levels of E-cadherin and pro-apoptotic marker Bim.
Conclusion
Mito-FF, designed for mitochondrial targeting and visualization, exhibited potent anticancer effects when combined with paclitaxel, in the breast cancer cells.
2.Synergistic anticancer effects of mitochondria-targeting peptide combined with paclitaxel in breast cancer cells: a preclinical study
Juneyoung AHN ; Ok-Hee KIM ; Seongeon JIN ; Ja-Hyoung RYU ; Dosang LEE ; Woo-Chan PARK ; Say-June KIM
Annals of Surgical Treatment and Research 2025;108(2):108-123
Purpose:
Mitochondria-accumulating amphiphilic peptide (Mito-FF) was designed to selectively target mitochondria in cancer cells and enhance anticancer effects through its unique structure. Mito-FF consists of (1) diphenylalanine, a β-sheet-forming building block critical for self-assembly; (2) triphenylphosphonium, a mitochondrial targeting moiety guiding the peptide to mitochondria; and (3) pyrene, a fluorescent probe enabling visualization of its accumulation and selfassembly. This study evaluates the anticancer efficacy of Mito-FF in breast cancer cells and explores its combination with paclitaxel, a standard therapy for breast cancer, focusing on its modulation of the epithelial-mesenchymal transition (EMT) pathway.
Methods:
In vitro and in vivo experiments were performed using MCF-7 and MDA-MB-231 breast cancer cell lines and their respective xenograft models. Cell viability, migration, EMT marker expression, and apoptosis-related proteins were analyzed.
Results:
Mito-FF demonstrated superior inhibition of cell viability and migration compared to paclitaxel alone in both cell lines. Combination therapy with Mito-FF and paclitaxel resulted in enhanced reduction of cell viability and migration. EMT markers were significantly modulated, with decreased mesenchymal markers (Snail and vimentin) and increased epithelial marker (E-cadherin) following combination treatment. Furthermore, the combination therapy synergistically elevated proapoptotic markers such as poly (adenosine diphosphate-ribose) polymerase and reduced anti-apoptotic markers such as myeloid cell leukemia 1. In vivo experiments revealed a marked reduction in tumor volume with combination therapy, accompanied by the highest expression levels of E-cadherin and pro-apoptotic marker Bim.
Conclusion
Mito-FF, designed for mitochondrial targeting and visualization, exhibited potent anticancer effects when combined with paclitaxel, in the breast cancer cells.
3.Synergistic anticancer effects of mitochondria-targeting peptide combined with paclitaxel in breast cancer cells: a preclinical study
Juneyoung AHN ; Ok-Hee KIM ; Seongeon JIN ; Ja-Hyoung RYU ; Dosang LEE ; Woo-Chan PARK ; Say-June KIM
Annals of Surgical Treatment and Research 2025;108(2):108-123
Purpose:
Mitochondria-accumulating amphiphilic peptide (Mito-FF) was designed to selectively target mitochondria in cancer cells and enhance anticancer effects through its unique structure. Mito-FF consists of (1) diphenylalanine, a β-sheet-forming building block critical for self-assembly; (2) triphenylphosphonium, a mitochondrial targeting moiety guiding the peptide to mitochondria; and (3) pyrene, a fluorescent probe enabling visualization of its accumulation and selfassembly. This study evaluates the anticancer efficacy of Mito-FF in breast cancer cells and explores its combination with paclitaxel, a standard therapy for breast cancer, focusing on its modulation of the epithelial-mesenchymal transition (EMT) pathway.
Methods:
In vitro and in vivo experiments were performed using MCF-7 and MDA-MB-231 breast cancer cell lines and their respective xenograft models. Cell viability, migration, EMT marker expression, and apoptosis-related proteins were analyzed.
Results:
Mito-FF demonstrated superior inhibition of cell viability and migration compared to paclitaxel alone in both cell lines. Combination therapy with Mito-FF and paclitaxel resulted in enhanced reduction of cell viability and migration. EMT markers were significantly modulated, with decreased mesenchymal markers (Snail and vimentin) and increased epithelial marker (E-cadherin) following combination treatment. Furthermore, the combination therapy synergistically elevated proapoptotic markers such as poly (adenosine diphosphate-ribose) polymerase and reduced anti-apoptotic markers such as myeloid cell leukemia 1. In vivo experiments revealed a marked reduction in tumor volume with combination therapy, accompanied by the highest expression levels of E-cadherin and pro-apoptotic marker Bim.
Conclusion
Mito-FF, designed for mitochondrial targeting and visualization, exhibited potent anticancer effects when combined with paclitaxel, in the breast cancer cells.
4.Remaining life expectancy of Korean hemodialysis patients: how much longer can they live?
Hayne Cho PARK ; Do Hyoung KIM ; AJin CHO ; Bo Yeon KIM ; Miri LEE ; Gui Ok KIM ; Jinseog KIM ; Young-Ki LEE
Kidney Research and Clinical Practice 2024;43(5):671-679
Hemodialysis (HD) patients have a higher mortality rate compared to the general population. However, no study has investigated life expectancy in Korean HD patients so far. Therefore, this study aimed to calculate the remaining life expectancy among Korean maintenance HD patients and compare it to those of the general population as well as HD patients from other countries. Methods: Baseline data were retrieved from HD quality assessment data from 2015. Among the patients over 30 years old who were alive at the beginning of 2016 (20,304 males and 14,264 females), a total of 22,078 (12,621 males and 9,457 females) were still alive at the end of 2021 while 12,490 (7,683 males and 4,807 females) were deceased during 6 years of follow-up. We used the life table method to calculate the expected remaining years of life in 2-year increments. Results: The remaining life expectancies for 60-year-old patients were 11.64 years for males and 14.64 years for females. The average remaining life expectancies of the HD population were only about half of the general population. Diabetic patients demonstrated shorter life expectancy compared to patients with hypertension or glomerulonephritis. The remaining life expectancy of Korean HD patients was similar to that of Japanese and was almost double that of HD patients in Western countries such as Europe and the United States. Conclusion: The HD population shows a shorter life expectancy compared to the general population. Longitudinal analysis should be warranted to analyze the effect of advanced dialysis technology on improved survival rates among the HD population.
5.Sex-Specific Susceptibility Loci Associated With Coronary Artery Aneurysms in Patients With Kawasaki Disease
Jae-Jung KIM ; Young Mi HONG ; Sin Weon YUN ; Kyung-Yil LEE ; Kyung Lim YOON ; Myung-Ki HAN ; Gi Beom KIM ; Hong-Ryang KIL ; Min Seob SONG ; Hyoung Doo LEE ; Kee Soo HA ; Hyun Ok JUN ; Jeong Jin YU ; Gi Young JANG ; Jong-Keuk LEE ;
Korean Circulation Journal 2024;54(9):577-586
Background and Objectives:
Kawasaki disease (KD) is an acute vasculitis that primarily affects children under age 5 years. Approximately 20–25% of untreated children with KD and 3–5% of those treated with intravenous immunoglobulin therapy develop coronary artery aneurysms (CAAs). The prevalence of CAAs is much higher in male than in female patients with KD, but the underlying factors contributing to susceptibility to CAAs in patients with KD remain unclear. This study aimed to identify sex-specific susceptibility loci associated with CAAs in KD patients.
Methods:
A sex-stratified genome-wide association study (GWAS) was performed using previously obtained GWAS data from 296 KD patients and a new replication study in an independent set of 976 KD patients by comparing KD patients without CAA (controls) and KD patients with aneurysms (internal diameter ≥5 mm) (cases).
Results:
Six male-specific susceptibility loci, PDE1C, NOS3, DLG2, CPNE8, FUNDC1, and GABRQ (odds ratios [ORs], 2.25–9.98; p=0.00204–1.96×10−6 ), and 2 female-specific susceptibility loci, SMAD3 (OR, 4.59; p=0.00016) and IL1RAPL1 (OR, 4.35; p=0.00026), were significantly associated with CAAs in patients with KD. In addition, the numbers of CAA risk alleles additively contributed to the development of CAAs in patients with KD.
Conclusions
A sex-stratified GWAS identified 6 male-specific (PDE1C, NOS3, DLG2, CPNE8, FUNDC1, and GABRQ) and 2 female-specific (SMAD3 and IL1RAPL1) CAA susceptibility loci in patients with KD.
6.Comparison of Statin With Ezetimibe Combination Therapy Versus Statin Monotherapy for Primary Prevention in Middle-Aged Adults
Jung-Joon CHA ; Soon Jun HONG ; Subin LIM ; Ju Hyeon KIM ; Hyung Joon JOO ; Jae Hyoung PARK ; Cheol Woong YU ; Do-Sun LIM ; Jang Young KIM ; Jin-Ok JEONG ; Jeong-Hun SHIN ; Chi Young SHIM ; Jong-Young LEE ; Young-Hyo LIM ; Sung Ha PARK ; Eun Joo CHO ; Hasung KIM ; Jungkuk LEE ; Ki-Chul SUNG ;
Korean Circulation Journal 2024;54(9):534-544
Background and Objectives:
Lipid lowering therapy is essential to reduce the risk of major cardiovascular events; however, limited evidence exists regarding the use of statin with ezetimibe as primary prevention strategy for middle-aged adults. We aimed to investigate the impact of single pill combination therapy on clinical outcomes in relatively healthy middleaged patients when compared with statin monotherapy.
Methods:
Using the Korean National Health Insurance Service database, a propensity score match analysis was performed for baseline characteristics of 92,156 patients categorized into combination therapy (n=46,078) and statin monotherapy (n=46,078) groups. Primary outcome was composite outcomes, including death, coronary artery disease, and ischemic stroke. And secondary outcome was all-cause death. The mean follow-up duration was 2.9±0.3 years.
Results:
The 3-year composite outcomes of all-cause death, coronary artery disease, and ischemic stroke demonstrated no significant difference between the 2 groups (10.3% vs.10.1%; hazard ratio [HR], 1.022; 95% confidence interval [CI], 0.980–1.064; p=0.309).Meanwhile, the 3-year all-cause death rate was lower in the combination therapy group than in the statin monotherapy group (0.2% vs. 0.4%; p<0.001), with a significant HR of 0.595 (95% CI, 0.460–0.769; p<0.001). Single pill combination therapy exhibited consistently lower mortality rates across various subgroups.
Conclusions
Compared to the statin monotherapy, the combination therapy for primary prevention showed no difference in composite outcomes but may reduce mortality risk in relatively healthy middle-aged patients. However, since the study was observational, further randomized clinical trials are needed to confirm these findings.
7.Remaining life expectancy of Korean hemodialysis patients: how much longer can they live?
Hayne Cho PARK ; Do Hyoung KIM ; AJin CHO ; Bo Yeon KIM ; Miri LEE ; Gui Ok KIM ; Jinseog KIM ; Young-Ki LEE
Kidney Research and Clinical Practice 2024;43(5):671-679
Hemodialysis (HD) patients have a higher mortality rate compared to the general population. However, no study has investigated life expectancy in Korean HD patients so far. Therefore, this study aimed to calculate the remaining life expectancy among Korean maintenance HD patients and compare it to those of the general population as well as HD patients from other countries. Methods: Baseline data were retrieved from HD quality assessment data from 2015. Among the patients over 30 years old who were alive at the beginning of 2016 (20,304 males and 14,264 females), a total of 22,078 (12,621 males and 9,457 females) were still alive at the end of 2021 while 12,490 (7,683 males and 4,807 females) were deceased during 6 years of follow-up. We used the life table method to calculate the expected remaining years of life in 2-year increments. Results: The remaining life expectancies for 60-year-old patients were 11.64 years for males and 14.64 years for females. The average remaining life expectancies of the HD population were only about half of the general population. Diabetic patients demonstrated shorter life expectancy compared to patients with hypertension or glomerulonephritis. The remaining life expectancy of Korean HD patients was similar to that of Japanese and was almost double that of HD patients in Western countries such as Europe and the United States. Conclusion: The HD population shows a shorter life expectancy compared to the general population. Longitudinal analysis should be warranted to analyze the effect of advanced dialysis technology on improved survival rates among the HD population.
8.Sex-Specific Susceptibility Loci Associated With Coronary Artery Aneurysms in Patients With Kawasaki Disease
Jae-Jung KIM ; Young Mi HONG ; Sin Weon YUN ; Kyung-Yil LEE ; Kyung Lim YOON ; Myung-Ki HAN ; Gi Beom KIM ; Hong-Ryang KIL ; Min Seob SONG ; Hyoung Doo LEE ; Kee Soo HA ; Hyun Ok JUN ; Jeong Jin YU ; Gi Young JANG ; Jong-Keuk LEE ;
Korean Circulation Journal 2024;54(9):577-586
Background and Objectives:
Kawasaki disease (KD) is an acute vasculitis that primarily affects children under age 5 years. Approximately 20–25% of untreated children with KD and 3–5% of those treated with intravenous immunoglobulin therapy develop coronary artery aneurysms (CAAs). The prevalence of CAAs is much higher in male than in female patients with KD, but the underlying factors contributing to susceptibility to CAAs in patients with KD remain unclear. This study aimed to identify sex-specific susceptibility loci associated with CAAs in KD patients.
Methods:
A sex-stratified genome-wide association study (GWAS) was performed using previously obtained GWAS data from 296 KD patients and a new replication study in an independent set of 976 KD patients by comparing KD patients without CAA (controls) and KD patients with aneurysms (internal diameter ≥5 mm) (cases).
Results:
Six male-specific susceptibility loci, PDE1C, NOS3, DLG2, CPNE8, FUNDC1, and GABRQ (odds ratios [ORs], 2.25–9.98; p=0.00204–1.96×10−6 ), and 2 female-specific susceptibility loci, SMAD3 (OR, 4.59; p=0.00016) and IL1RAPL1 (OR, 4.35; p=0.00026), were significantly associated with CAAs in patients with KD. In addition, the numbers of CAA risk alleles additively contributed to the development of CAAs in patients with KD.
Conclusions
A sex-stratified GWAS identified 6 male-specific (PDE1C, NOS3, DLG2, CPNE8, FUNDC1, and GABRQ) and 2 female-specific (SMAD3 and IL1RAPL1) CAA susceptibility loci in patients with KD.
9.Comparison of Statin With Ezetimibe Combination Therapy Versus Statin Monotherapy for Primary Prevention in Middle-Aged Adults
Jung-Joon CHA ; Soon Jun HONG ; Subin LIM ; Ju Hyeon KIM ; Hyung Joon JOO ; Jae Hyoung PARK ; Cheol Woong YU ; Do-Sun LIM ; Jang Young KIM ; Jin-Ok JEONG ; Jeong-Hun SHIN ; Chi Young SHIM ; Jong-Young LEE ; Young-Hyo LIM ; Sung Ha PARK ; Eun Joo CHO ; Hasung KIM ; Jungkuk LEE ; Ki-Chul SUNG ;
Korean Circulation Journal 2024;54(9):534-544
Background and Objectives:
Lipid lowering therapy is essential to reduce the risk of major cardiovascular events; however, limited evidence exists regarding the use of statin with ezetimibe as primary prevention strategy for middle-aged adults. We aimed to investigate the impact of single pill combination therapy on clinical outcomes in relatively healthy middleaged patients when compared with statin monotherapy.
Methods:
Using the Korean National Health Insurance Service database, a propensity score match analysis was performed for baseline characteristics of 92,156 patients categorized into combination therapy (n=46,078) and statin monotherapy (n=46,078) groups. Primary outcome was composite outcomes, including death, coronary artery disease, and ischemic stroke. And secondary outcome was all-cause death. The mean follow-up duration was 2.9±0.3 years.
Results:
The 3-year composite outcomes of all-cause death, coronary artery disease, and ischemic stroke demonstrated no significant difference between the 2 groups (10.3% vs.10.1%; hazard ratio [HR], 1.022; 95% confidence interval [CI], 0.980–1.064; p=0.309).Meanwhile, the 3-year all-cause death rate was lower in the combination therapy group than in the statin monotherapy group (0.2% vs. 0.4%; p<0.001), with a significant HR of 0.595 (95% CI, 0.460–0.769; p<0.001). Single pill combination therapy exhibited consistently lower mortality rates across various subgroups.
Conclusions
Compared to the statin monotherapy, the combination therapy for primary prevention showed no difference in composite outcomes but may reduce mortality risk in relatively healthy middle-aged patients. However, since the study was observational, further randomized clinical trials are needed to confirm these findings.
10.Remaining life expectancy of Korean hemodialysis patients: how much longer can they live?
Hayne Cho PARK ; Do Hyoung KIM ; AJin CHO ; Bo Yeon KIM ; Miri LEE ; Gui Ok KIM ; Jinseog KIM ; Young-Ki LEE
Kidney Research and Clinical Practice 2024;43(5):671-679
Hemodialysis (HD) patients have a higher mortality rate compared to the general population. However, no study has investigated life expectancy in Korean HD patients so far. Therefore, this study aimed to calculate the remaining life expectancy among Korean maintenance HD patients and compare it to those of the general population as well as HD patients from other countries. Methods: Baseline data were retrieved from HD quality assessment data from 2015. Among the patients over 30 years old who were alive at the beginning of 2016 (20,304 males and 14,264 females), a total of 22,078 (12,621 males and 9,457 females) were still alive at the end of 2021 while 12,490 (7,683 males and 4,807 females) were deceased during 6 years of follow-up. We used the life table method to calculate the expected remaining years of life in 2-year increments. Results: The remaining life expectancies for 60-year-old patients were 11.64 years for males and 14.64 years for females. The average remaining life expectancies of the HD population were only about half of the general population. Diabetic patients demonstrated shorter life expectancy compared to patients with hypertension or glomerulonephritis. The remaining life expectancy of Korean HD patients was similar to that of Japanese and was almost double that of HD patients in Western countries such as Europe and the United States. Conclusion: The HD population shows a shorter life expectancy compared to the general population. Longitudinal analysis should be warranted to analyze the effect of advanced dialysis technology on improved survival rates among the HD population.

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