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.Medication Adherence in Korean Patients with Inflammatory Bowel Disease and Its Associated Factors
Kyunghwan OH ; Eun Ja KWON ; Jeong Hye KIM ; Kyuwon KIM ; Jae Yong LEE ; Hee Seung HONG ; Seung Wook HONG ; Jin Hwa PARK ; Sung Wook HWANG ; Dong-Hoon YANG ; Byong Duk YE ; Jeong-Sik BYEON ; Seung-Jae MYUNG ; Suk-Kyun YANG ; Jeong Yun PARK ; Sang Hyoung PARK
The Ewha Medical Journal 2022;45(2):35-45
Objectives:
It is important that inflammatory bowel disease (IBD) patients adhere to their prescribed medication regimens to avoid the repeat exacerbations, complications, or surgeries associated with this disorder. However, there are few studies on medication adherence in patients with IBD, especially in Asian populations. So, we analyzed the factors associated with medication adherence in Korean IBD patients.
Methods:
Patients who had been diagnosed with Crohn’s disease (CD) or ulcerative colitis (UC) more than 6 months previously and receiving oral medications for IBD were enrolled. Medication adherence was measured using the Medical Adherence Reporting Scale (MARS-5), a self-reported medication adherence measurement tool.
Results:
Among 207 patients in the final study population, 125 (60.4%) had CD and 134 (64.7%) were men. The mean age was 39.63 years (SD, 13.16 years) and the mean disease duration was 10.09 years (SD, 6.33 years). The mean medication adherence score was 22.46 (SD, 2.86) out of 25, and 181 (87.4%) patients had score of 20 or higher.In multiple linear regression analysis, self-efficacy (β=0.341, P<0.001) and ≥3 dosing per day (β=–0.192 P=0.016) were revealed to be significant factors associated with medication adherence. Additionally, there was a positive correlation between self-efficacy and medication adherence (r=0.312, P<0.001). However, disease related knowledge, depression, and anxiety were not significantly associated with medication adherence.
Conclusion
To improve medication adherence among patients with IBD, a reduction in the number of doses per day and an improved self-efficacy will be helpful.
5.Predicting Responsiveness to Biofeedback Therapy Using High-resolution Anorectal Manometry With Integrated Pressurized Volume
Myeongsook SEO ; Jiyoung YOON ; Kee Wook JUNG ; Segyeong JOO ; Jungbok LEE ; Kyung Min CHOI ; Hyo Jeong LEE ; In Ja YOON ; Woojoo NOH ; So Young SEO ; Do Yeon KIM ; Sung Wook HWANG ; Sang Hyoung PARK ; Dong-Hoon YANG ; Byong Duk YE ; Jeong-Sik BYEON ; Suk-Kyun YANG ; Seung-Jae MYUNG
Journal of Neurogastroenterology and Motility 2022;28(4):608-617
Background/Aims:
Biofeedback therapy is widely used to treat patients with chronic constipation, especially those with dyssynergic defecation. Yet, the utility of high-resolution manometry with novel parameters in the prediction of biofeedback response has not been reported. Thus, we constructed a model for predicting biofeedback therapy responders by applying the concept of integrated pressurized volume in patients undergoing high-resolution anorectal manometry.
Methods:
Seventy-one female patients (age: 48-68 years) with dyssynergic defecation who underwent initial high-resolution anorectal manometry and subsequent biofeedback therapy were enrolled. The manometry profiles were used to calculate the 3-dimensional integrated pressurized volumes by multiplying the distance, time, and amplitude during simulated evacuation. Partial least squares regression was performed to generate a predictive model for responders to biofeedback therapy by using the integrated pressurized volume parameters.
Results:
Fifty-five (77.5%) patients responded to biofeedback therapy. The responders and non-responders did not show significant differences in the conventional manometric parameters. The partial least squares regression model used a linear combination of eight integrated pressurized volume parameters and generated an area under the curve of 0.84 (95% confidence interval: 0.76-0.95, P < 0.01), with 85.5% sensitivity and 62.1% specificity.
Conclusions
Integrated pressurized volume parameters were better than conventional parameters in predicting the responsiveness to biofeedback therapy, and the combination of these parameters and partial least squares regression was particularly promising. Integrated pressurized volume parameters can more effectively explain the physiology of the anorectal canal compared with conventional parameters.
6.Clinicopathological Characteristics and Surgical Outcomes of Crohn Disease-Associated Colorectal Malignancy
Yoo Na LEE ; Jong Lyul LEE ; Chang Sik YU ; Jong Beom KIM ; Seok-Byung LIM ; In Ja PARK ; Young Sik YOON ; Chan Wook KIM ; Suk-Kyun YANG ; Byong Duk YE ; Sang Hyoung PARK ; Jin Cheon KIM
Annals of Coloproctology 2021;37(2):101-108
Purpose:
Carcinoma arising from Crohn disease (CD) is rare, and there is no clear guidance on how to properly screen for at-risk patients and choose appropriate care. This study aimed to evaluate the clinicopathological characteristics, treatment, and oncologic outcomes of CD patients diagnosed with colorectal cancer (CRC).
Methods:
Using medical records, we retrospectively enrolled a single-center cohort of 823 patients who underwent abdominal surgery for CD between January 2006 and December 2015. CD-associated CRC patients included those with adenocarcinoma, lymphoma, or neuroendocrine tumors of the colon and rectum.
Results:
Nineteen patients (2.3%) underwent abdominal surgery to treat CD-associated CRC. The mean duration of CD in the CD-associated CRC group was significantly longer than that in the benign CD group (124.7 ± 77.7 months vs. 68.9 ± 60.2 months, P = 0.006). The CD-associated CRC group included a higher proportion of patients with a history of perianal disease (73.7% vs. 50.2%, P = 0.035) and colonic location (47.4% vs. 6.5%, P = 0.001). Among 19 CD-associated CRC patients, 17 (89.5%) were diagnosed with adenocarcinoma, and of the 17 cases, 15 (88.2%) were rectal adenocarcinoma. On multivariable analyses for developing CRC, only colonic location was a risk factor (relative risk, 7.735; 95% confidence interval, 2.862–20.903; P = 0.001).
Conclusion
Colorectal malignancy is rare among CD patients, even among patients who undergo abdominal surgery. Rectal adenocarcinoma accounted for most of the CRC, and colonic location was a risk factor for developing CRC.
7.Multicenter retrospective analysis of patients with chronic lymphocytic leukemia in Korea
Jun Ho YI ; Gyeong-Won LEE ; Ji Hyun LEE ; Kwai Han YOO ; Chul Won JUNG ; Dae Sik KIM ; Jeong-Ok LEE ; Hyeon Seok EOM ; Ja Min BYUN ; Youngil KOH ; Sung Soo YOON ; Jin Seok KIM ; Jee Hyun KONG ; Ho-Young YHIM ; Deok-Hwan YANG ; Dok Hyun YOON ; Do Hyoung LIM ; Won-Sik LEE ; Ho-Jin SHIN
Blood Research 2021;56(4):243-251
Background:
Chronic lymphocytic leukemia (CLL) is the most common type of adult leukemia in Western countries but is rare in the East Asian countries. Due to its rarity and the lack of feasible novel agents and laboratory prognostic tools, there are limited data on the clinical outcomes of this disease in Asia. To clarify the current treatment status, we performed a multicenter retrospective analysis of patients with CLL in Korea.
Methods:
The medical records of 192 eligible patients between 2008 and 2019 were reviewed for clinical characteristics, treatment courses, and outcomes. The first-line treatment regimens of the patients included in this analysis were as follows: fludarabine/cyclophosphamide/rituximab (FCR) (N=117, 52.7%), obinutuzumab plus chlorambucil (GC) (N=30, 13.5%), and chlorambucil monotherapy (N=24, 10.8%).
Results:
The median progression-free survival (PFS) was 55.6 months, and the average 2-year PFS rate was 80.3%. PFS was not significantly different between the patients receiving FCR and those receiving GC; however, chlorambucil treatment was associated with significantly inferior PFS (P <0.001). The median overall survival was 136.3 months, and the average 5- and 10-year OS rates were 82.0% and 57.4%, respectively.
Conclusion
This is one of the largest studies involving Korean patients with CLL. Although the patients had been treated with less favored treatment regimens, the outcomes were not different from those reported in Western studies.
8.Effects of the route of erythropoietin administration on hemoglobin variability and cardiovascular events in hemodialysis patients
Do Hyoung KIM ; Young-Ki LEE ; Juhee KIM ; Hayne Cho PARK ; Kyu Sang YUN ; AJin CHO ; Jong-Woo YOON ; Ja-Ryong KOO ; Jung-Woo NOH
Kidney Research and Clinical Practice 2021;40(4):724-733
Methods:
This is a post hoc analysis of a prospective, controlled, randomized, unblinded study with 78 Korean hemodialysis patients receiving intravenous (n = 40) or subcutaneous (n = 38) erythropoietin therapy. We evaluated hemoglobin variability by calculating the frequency of hemoglobin measurements outside the target range during all visits. The high-frequency group was defined by those with hemoglobin variability over the median value (25%) while the low-frequency group was defined by those with hemoglobin variability of <25%.
Results:
In this analysis, 37 patients (51.1%) were men, and the mean age was 50.6 ± 12.5 years. Twenty-five patients (35.2%) had diabetes mellitus. The frequency of the value being outside the target hemoglobin range was higher in the subcutaneous group compared to the intravenous group (0.36 ± 0.19 vs. 0.27 ± 0.12/visit, p = 0.03). The low-frequency group required significantly lower erythropoietin doses compared to the high-frequency group. In the adjusted Cox analysis, the parameter high-frequency group was a significant independent risk factor for cardiovascular events (hazard ratio, 3.53; 95% confidence interval, 1.15–10.83; p = 0.03).
Conclusion
The risk of missing the target hemoglobin range increased with subcutaneous administration compared with intravenous erythropoietin administration in hemodialysis patients. An increased frequency of the value being outside the target hemoglobin range was also associated with an increased risk of cardiovascular events.
9.Forensic Microbiological Analysis for Vaginal Fluid Identification Using Multiplex Real-Time PCR System
Jeongyong KIM ; Min Ho LEE ; Hyojeong KIM ; Ja Hyun LEE ; Youn-Hyoung NAM ; Hyo Sook KIM ; Hyun Kyu YOON ; Ki Min SEONG ; Eungsoo KIM
Korean Journal of Legal Medicine 2021;45(1):14-21
Numerous methods for human body fluid identification using microbiological markers specific to different human body parts are well-established in forensic science. However, method for vaginal fluid screening have not been standardized yet. Therefore, in this study, a real-time polymerase chain reaction based assay for vaginal fluid identification was devised using bacteria residing in human vagina. This method employed three markers, namely Lactobacillus iners, Lactobacillus crispatus, and Bacteroides fragilis. L. iners and L. crispatus were chosen due to their high abundance in the vagina, whereas B. fragilis resides in the rectum. To examine the suitability of the new method for forensic microbial applications, a study of the distribution of vaginal flora in 143 Korean women was performed, along with characterization of the specificity, and performance of the new assay. Additionally, a casework study based on 130, 21, 20 and 17 DNA samples collected from the vagina, anus, saliva, blood, respectively, was carried out. L. iners (80.4%) and L. crispatus (55.2%) were detected with high abundance in the vagina of Korean women. The specificity of these markers was verified using microbial DNA from 23 species. This method could detect at least 1,000 copies/µL of microorganisms for all markers, thereby highlighting its robust sensitivity for vaginal fluid identification. The casework study confirmed these findings, with 89.2% (116/130) detection of vaginal fluid-derived DNA samples, and no false positives identified from the other sources studied. In conclusion, the developed method is expected to be efficient for preliminary microbiological analysis of vaginal samples in forensics.
10.A Study on the Usefulness of Postmortem Diabetes Mellitus-Related Tests
Hyoung Joo SON ; Hye Won SHIN ; Jong-Pil PARK ; Kyung-moo YANG ; Dong Ja KIM ; Nan Young LEE ; Kyunghong LEE
Korean Journal of Legal Medicine 2020;44(4):150-156
Diabetes mellitus (DM) is a group of metabolic disorders, that have become a major cause of death worldwide. This study aimed to determine the usefulness of diabetes-related laboratory tests for diagnosis of postmortem DM. From March to August 2018, among the autopsy cases investigated by the National Forensic Service, heart blood and vitreous humor samples from 253 cases that had not been decomposed were collected, and the data from 208 cases except 45 cases that were incapable of testing were analyzed for statistical significance and compared with the causes of death on autopsy reports. The levels of C-peptide, insulin, acetoacetate, β-hydroxybutyrate (β-HA), total ketone, and HbA1c were measured in the heart blood, and the levels of glucose, blood urea nitrogen, creatinine, and potassium were measured in the vitreous humor. The levels of glucose in the vitreous humor and HbA1c, β-HA, and total ketone in the heart blood were significantly correlated. C-peptide and insulin levels were lower than normal levels in most cases (C-peptide 92.3%, P=0.480, insulin 97.6%, P=0.589), and were not useful measures indicating diabetic complications. In the group with DM history, the average levels of HbA1c from the heart blood and glucose from the vitreous humor were higher than in those with no or unknown history of DM, indicating their usefulness as diagnostic tools. The results of this study suggest a postmortem DM diagnosis model.Therefore, postmortem DM-related tests can help diagnose the cause of death in forensic medicine.

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