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.Donor sex and donor-recipient sex disparity do not affect hepatocellular carcinoma recurrence after living donor liver transplantation
Rak Kyun OH ; Shin HWANG ; Gi-Won SONG ; Chul-Soo AHN ; Deok-Bog MOON ; Tae-Yong HA ; Dong-Hwan JUNG ; Gil-Chun PARK ; Young-In YOON ; Woo-Hyoung KANG
Annals of Surgical Treatment and Research 2023;105(3):133-140
Purpose:
Studies have yielded contradictory results on whether donor sex and donor-recipient sex disparity affect hepatocellular carcinoma (HCC) recurrence after living donor liver transplantation (LDLT). The present study assessed whether donor sex or donor-recipient sex disparity affects HCC recurrence after LDLT at a high-volume center.
Methods:
This study included 772 HCC patients who underwent LDLT between January 2006 and December 2015 at Asan Medical Center. Patients were divided into 4 groups based on the sex of the donor and recipient: male-to-male (n = 490, 63.5%), male-to-female (n = 75, 9.7%), female-to-male (n = 170, 22.0%), and female-to-female (n = 37, 4.8%).
Results:
Disease-free survival (DFS; P = 0.372) and overall survival (OS; P = 0.591) did not differ significantly among the 4 groups. DFS also did not differ significantly between LDLT recipients with male and female donors (P = 0.792) or between male and female recipients (P = 0.084). After patient matching with an α-FP/des-γ-carboxy prothrombin/tumor volume score cutoff of 5logs, donor-recipient sex disparity did not significantly affect DFS (P = 0.598) or OS (P = 0.777). There were also no differences in DFS in matched LDLT recipients with male and female donors (P = 0.312) or between male and female recipients (P = 0.374).
Conclusion
Neither donor sex nor donor-recipient sex disparity significantly affected posttransplant HCC recurrence.
5.Short-Term Outcomes of Laparoscopic Proximal Gastrectomy With DoubleTract Reconstruction Versus Laparoscopic Total Gastrectomy for Upper Early Gastric Cancer: A KLASS 05Randomized Clinical Trial
Sun-Hwi HWANG ; Do Joong PARK ; Hyung-Ho KIM ; Woo Jin HYUNG ; Hoon HUR ; Han-Kwang YANG ; Hyuk-Joon LEE ; Hyoung-Il KIM ; Seong-Ho KONG ; Young Woo KIM ; Han Hong LEE ; Beom Su KIM ; Young-Kyu PARK ; Young-Joon LEE ; Sang-Hoon AHN ; In-Seob LEE ; Yun-Suhk SUH ; Ji-Ho PARK ; Soyeon AHN ; Sang-Uk HAN
Journal of Gastric Cancer 2022;22(2):94-106
Purpose:
Laparoscopic proximal gastrectomy with double-tract reconstruction (LPG-DTR) is a function-preserving procedure performed for treating upper early gastric cancer (EGC).However, few studies have compared the outcomes of LPG-DTR with those of laparoscopic total gastrectomy (LTG). This study aimed at comparing the short-term outcomes of LPGDTR between LTG and upper EGC.
Materials and Methods:
For upper-third EGC, a multicenter, prospective, randomized trial was performed to compare those who underwent LPG-DTR with those who underwent LTG. Short-term outcomes, including clinicopathologic results, morbidity, mortality, and postoperative courses, were evaluated using a full analysis set based on the intention-to-treat principle and the per-protocol set.
Results:
Of the patients, 138 who fulfilled the criteria were randomized to each group. One patient in the LPG-DTR group withdrew consent. Sixty-eight patients underwent LPGDTR and 69 underwent LTG. The operative time (LPG-DTR=219.4 minutes; LTG=201.8 minutes; P=0.085), estimated blood loss (LPG-DTR=76.0 mL; LTG=66.1 mL; P=0.413), and the morbidity rate (LPG-DTR=23.5%; LTG=17.4%; P=0.373) between the groups were not significantly different. No mortality occurred in either of the study groups. Two weeks post operation, the Visick scores for postprandial symptoms, including reflux symptoms, were not significantly different between the groups (P=0.749). Laboratory findings on postoperative day 5 were not significantly different between the groups.
Conclusions
The short-term outcomes of LPG-DTR for upper EGC were comparable to those of LTG.Trial Registration: ClinicalTrials.gov Identifier: NCT02892643
6.Fates of retained hepatic segment IV and its prognostic impact in adult split liver transplantation using an extended right liver graft
Yong-Kyu CHUNG ; Shin HWANG ; Chul-Soo AHN ; Ki-Hun KIM ; Deok-Bog MOON ; Tae-Yong HA ; Gi-Won SONG ; Dong-Hwan JUNG ; Gil-Chun PARK ; Young-In YOON ; Woo-Hyoung KANG ; Hwui-Dong CHO ; Jin Uk CHOI ; Minjae KIM ; Sang Hoon KIM ; Byeong-Gon NA ; Sung-Gyu LEE
Annals of Surgical Treatment and Research 2021;101(1):37-48
Purpose:
When splitting a liver for adult and pediatric graft recipients, the retained left medial section (S4) will undergo ischemic necrosis and the right trisection graft becomes an extended right liver (ERL) graft. We investigated the fates of the retained S4 and its prognostic impact in adult split liver transplantation (SLT) using an ERL graft.
Methods:
This was a retrospective analysis of 25 adult SLT recipients who received split ERL grafts.
Results:
The mean model for end-stage liver disease (MELD) score was 27.3 ± 10.9 and graft-recipient weight ratio (GRWR) was 1.98 ± 0.44. The mean donor age was 26.5 ± 7.7 years. The split ERL graft weight was 1,181.5 ± 252.8 g, which resulted in a mean GRWR of 1.98 ± 0.44. Computed tomography of the retained S4 parenchyma revealed small ischemic necrosis in 16 patients (64.0%) and large ischemic necrosis in the remaining 9 patients (36.0%). No S4-associated biliary complications were developed. The mean GRWR was 1.87 ± 0.43 in the 9 patients with large ischemic necrosis and 2.10 ± 0.44 in the 15 cases with small ischemic necrosis (P = 0.283). The retained S4 parenchyma showed gradual atrophy on follow-up imaging studies. The amount of S4 ischemic necrosis was not associated with graft (P = 0.592) or patient (P = 0.243) survival. A MELD score of >30 and pretransplant ventilator support were associated with inferior outcomes.
Conclusion
The amount of S4 ischemic necrosis is not a prognostic factor in adult SLT recipients, probably due to a sufficiently large GRWR.
7.Atypical Teratoid/Rhabdoid Tumor of the Central Nervous System in Children under the Age of 3 Years
Meerim PARK ; Jung Woo HAN ; Seung Min HAHN ; Jun Ah LEE ; Joo-Young KIM ; Sang Hoon SHIN ; Dong-Seok KIM ; Hong In YOON ; Kyung Taek HONG ; Jung Yoon CHOI ; Hyoung Jin KANG ; Hee Young SHIN ; Ji Hoon PHI ; Seung-Ki KIM ; Ji Won LEE ; Keon Hee YOO ; Ki Woong SUNG ; Hong Hoe KOO ; Do Hoon LIM ; Hyung Jin SHIN ; Hyery KIM ; Kyung-Nam KOH ; Ho Joon IM ; Seung Do AHN ; Young-Shin RA ; Hee-Jo BAEK ; Hoon KOOK ; Tae-Young JUNG ; Hyoung Soo CHOI ; Chae-Yong KIM ; Hyeon Jin PARK ; Chuhl Joo LYU
Cancer Research and Treatment 2021;53(2):378-388
Purpose:
Atypical teratoid/rhabdoid tumor (ATRT) is a highly aggressive malignancy with peak incidence in children aged less than 3 years. Standard treatment for central nervous system ATRT in children under the age of 3 years have not been established yet. The objective of this study was to analyze characteristics and clinical outcomes of ATRT in children aged less than 3 years.
Materials and Methods:
A search of medical records from seven centers was performed between January 2005 and December 2016.
Results:
Forty-three patients were enrolled. With a median follow-up of 90 months, 27 patients (64.3%) showed at least one episode of disease progression (PD). The first date of PD was at 160 days after diagnosis. The 1- and 3-year progression-free survivals (PFS) were 51.2% and 28.5%, respectively. The 1- and 3-year overall survivals were 61.9% and 38.1%, respectively. The 3-year PFS was improved from 0% in pre-2011 to 47.4% in post-2011. Excluding one patient who did not receive any further therapy after surgery, 27 patients died due to PD (n=21), treatment-related toxicity (n=5), or unknown cause (n=1). In univariate analysis, factors associated with higher 3-year PFS were no metastases, diagnosis after 2011, early adjuvant radiotherapy, and high-dose chemotherapy (HDCT). In multivariate analysis, the use of HDCT and adjuvant radiotherapy remained significant prognostic factors for PFS (both p < 0.01).
Conclusion
Aggressive therapy including early adjuvant radiotherapy and HDCT could be considered to improve outcomes of ATRT in children under the age of 3 years.
8.Development and Validation of a Symptom-Focused Quality of Life Questionnaire (KOQUSS-40) for Gastric Cancer Patients after Gastrectomy
Bang Wool EOM ; Joongyub LEE ; In Seob LEE ; Young-Gil SON ; Keun Won RYU ; Sung Geun KIM ; Hyoung-Il KIM ; Young-Woo KIM ; Seong-Ho KONG ; Oh Kyoung KWON ; Ji-Ho PARK ; Ji Yeong AN ; Chang Hyun KIM ; Byoung-Jo SUH ; Hong Man YOON ; Myoung Won SON ; Ji Yeon PARK ; Jong-Min PARK ; Sang-Ho JEONG ; Moon-Won YOO ; Geum Jong SONG ; Han-Kwang YANG ; Yun-Suhk SUH ; Ki Bum PARK ; Sang-Hoon AHN ; Dong Woo SHIN ; Ye Seob JEE ; Hye-Seong AHN ; Sol LEE ; Jae Seok MIN ; Haejin IN ; Ahyoung KIM ; Hoon HUR ; Hyuk-Joon LEE ;
Cancer Research and Treatment 2021;53(3):763-772
Purpose:
Patients who have undergone gastrectomy have unique symptoms that are not appropriately assessed using currently available tools. This study developed and validated a symptom-focused quality of life (QoL) questionnaire for patients who have received gastrectomy for gastric cancer. Materials and Methods Based on a literature review, patient interviews, and expert consultation by the KOrean QUality of life in Stomach cancer patients Study group (KOQUSS), the initial item pool was developed. Two large-scale developmental studies were then sequentially conducted for exploratory factor analyses for content validity and item reduction. The final item pool was validated in a separate cohort of patients and assessed for internal consistency, test-retest reliability, construct validity, and clinical validity.
Results
The initial questionnaire consisted of 46-items in 12 domains. Data from 465 patients at 11 institutions, followed by 499 patients at 13 institutions, were used to conduct item reduction and exploratory factor analyses. The final questionnaire (KOQUSS-40) comprised 40 items within 11 domains. Validation of KOQUSS-40 was conducted on 413 patients from 12 hospitals. KOQUSS-40 was found to have good model fit. The mean summary score of the KOQUSS-40 was correlated with the EORTC QLQ-C30 and STO22 (correlation coefficients, 0.821 and 0.778, respectively). The KOQUSS-40 score was also correlated with clinical factors, and had acceptable internal consistency (> 0.7). Test-retest reliability was greater than 0.8. Conclusion The KOQUSS-40 can be used to assess QoL of gastric cancer patients after gastrectomy and allows for a robust comparison of surgical techniques in clinical trials.
9.What is the Cause of Recurrent Urinary Tract Infection? Contemporary Microscopic Concepts of Pathophysiology
Aram KIM ; Jaehak AHN ; Woo Suk CHOI ; Hyoung Keun PARK ; Sehwan KIM ; Sung Hyun PAICK ; Hyeong Gon KIM
International Neurourology Journal 2021;25(3):192-201
Urinary tract infections (UTIs) are the most common infectious disease and are mainly caused by Escherichia coli. In this review, we introduce the current concept of recurrent UTI (rUTI) based on recent research dealing with pathophysiology of the disease. Although urine is considered sterile, recent studies dealing with microbiome have proposed different ideas. UTIs have typically been considered as extracellular infections, but recently, uropathogenic Escherichia coli (UPEC) has been shown to bind and replicate in the urothelium to make intracellular bacterial communities. Binding UPECs might proceed in many ways including extracellular expulsion for clearance or survival and quiescent intracellular reservoirs that can cause rUTI. Moreover, it is also suggested that other important factors, such as lipopolysaccharide and multimicrobial infection, can be the cause of rUTI. This review article reveals a key mechanism of recurrence and discusses what makes a pathway of resolution or recurrence in a host after initial infection.
10.Fates of retained hepatic segment IV and its prognostic impact in adult split liver transplantation using an extended right liver graft
Yong-Kyu CHUNG ; Shin HWANG ; Chul-Soo AHN ; Ki-Hun KIM ; Deok-Bog MOON ; Tae-Yong HA ; Gi-Won SONG ; Dong-Hwan JUNG ; Gil-Chun PARK ; Young-In YOON ; Woo-Hyoung KANG ; Hwui-Dong CHO ; Jin Uk CHOI ; Minjae KIM ; Sang Hoon KIM ; Byeong-Gon NA ; Sung-Gyu LEE
Annals of Surgical Treatment and Research 2021;101(1):37-48
Purpose:
When splitting a liver for adult and pediatric graft recipients, the retained left medial section (S4) will undergo ischemic necrosis and the right trisection graft becomes an extended right liver (ERL) graft. We investigated the fates of the retained S4 and its prognostic impact in adult split liver transplantation (SLT) using an ERL graft.
Methods:
This was a retrospective analysis of 25 adult SLT recipients who received split ERL grafts.
Results:
The mean model for end-stage liver disease (MELD) score was 27.3 ± 10.9 and graft-recipient weight ratio (GRWR) was 1.98 ± 0.44. The mean donor age was 26.5 ± 7.7 years. The split ERL graft weight was 1,181.5 ± 252.8 g, which resulted in a mean GRWR of 1.98 ± 0.44. Computed tomography of the retained S4 parenchyma revealed small ischemic necrosis in 16 patients (64.0%) and large ischemic necrosis in the remaining 9 patients (36.0%). No S4-associated biliary complications were developed. The mean GRWR was 1.87 ± 0.43 in the 9 patients with large ischemic necrosis and 2.10 ± 0.44 in the 15 cases with small ischemic necrosis (P = 0.283). The retained S4 parenchyma showed gradual atrophy on follow-up imaging studies. The amount of S4 ischemic necrosis was not associated with graft (P = 0.592) or patient (P = 0.243) survival. A MELD score of >30 and pretransplant ventilator support were associated with inferior outcomes.
Conclusion
The amount of S4 ischemic necrosis is not a prognostic factor in adult SLT recipients, probably due to a sufficiently large GRWR.

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