1.Licochalcone C Inhibits the Growth of Human Colorectal Cancer HCT116 Cells Resistant to Oxaliplatin
Seung-On LEE ; Sang Hoon JOO ; Jin-Young LEE ; Ah-Won KWAK ; Ki-Taek KIM ; Seung-Sik CHO ; Goo YOON ; Yung Hyun CHOI ; Jin Woo PARK ; Jung-Hyun SHIM
Biomolecules & Therapeutics 2024;32(1):104-114
Licochalcone C (LCC; PubChem CID:9840805), a chalcone compound originating from the root of Glycyrrhiza inflata, has shown anticancer activity against skin cancer, esophageal squamous cell carcinoma, and oral squamous cell carcinoma. However, the therapeutic potential of LCC in treating colorectal cancer (CRC) and its underlying molecular mechanisms remain unclear. Chemotherapy for CRC is challenging because of the development of drug resistance. In this study, we examined the antiproliferative activity of LCC in human colorectal carcinoma HCT116 cells, oxaliplatin (Ox) sensitive and Ox-resistant HCT116 cells (HCT116-OxR). LCC significantly and selectively inhibited the growth of HCT116 and HCT116-OxR cells. An in vitro kinase assay showed that LCC inhibited the kinase activities of EGFR and AKT. Molecular docking simulations using AutoDock Vina indicated that LCC could be in ATP-binding pockets. Decreased phosphorylation of EGFR and AKT was observed in the LCC-treated cells. In addition, LCC induced cell cycle arrest by modulating the expression of cell cycle regulators p21, p27, cyclin B1, and cdc2. LCC treatment induced ROS generation in CRC cells, and the ROS induction was accompanied by the phosphorylation of JNK and p38 kinases. Moreover, LCC dysregulated mitochondrial membrane potential (MMP), and the disruption of MMP resulted in the release of cytochrome c into the cytoplasm and activation of caspases to execute apoptosis. Overall, LCC showed anticancer activity against both Ox-sensitive and Ox-resistant CRC cells by targeting EGFR and AKT, inducing ROS generation and disrupting MMP. Thus, LCC may be potential therapeutic agents for the treatment of Ox-resistant CRC cells.
2.Clinical Practice Guideline for Percutaneous Endoscopic Gastrostomy
Chung Hyun TAE ; Ju Yup LEE ; Moon Kyung JOO ; Chan Hyuk PARK ; Eun Jeong GONG ; Cheol Min SHIN ; Hyun LIM ; Hyuk Soon CHOI ; Miyoung CHOI ; Sang Hoon KIM ; Chul-Hyun LIM ; Jeong-Sik BYEON ; Ki-Nam SHIM ; Geun Am SONG ; Moon Sung LEE ; Jong-Jae PARK ; Oh Young LEE ;
Gut and Liver 2024;18(1):10-26
With an aging population, the number of patients with difficulty swallowing due to medical conditions is gradually increasing. In such cases, enteral nutrition is administered through a temporary nasogastric tube. Long-term use of a nasogastric tube leads to various complications and a decreased quality of life. Percutaneous endoscopic gastrostomy (PEG) is the percutaneous placement of a tube into the stomach, aided endoscopically, which may be an alternative to a nasogastric tube when enteral nutritional is required for 4 weeks or more. This paper is the first Korean clinical guideline for PEG. It was developed jointly by the Korean College of Helicobacter and Upper Gastrointestinal Research and led by the Korean Society of Gastrointestinal Endoscopy. These guidelines aimed to provide physicians, including endoscopists, with the indications, use of prophylactic antibiotics, timing of enteric nutrition, tube placement methods, complications, replacement, and tubes removal for PEG based on the currently available clinical evidence.
3.The Effect of Tegoprazan on the Treatment of Endoscopic Resection-Induced Artificial Ulcers: A Multicenter, Randomized, Active-Controlled Study
Byung-Wook KIM ; Jong Jae PARK ; Hee Seok MOON ; Wan Sik LEE ; Ki-Nam SHIM ; Gwang Ho BAIK ; Yun Jeong LIM ; Hang Lak LEE ; Young Hoon YOUN ; Jun Chul PARK ; In-Kyung SUNG ; Hyunsoo CHUNG ; Jeong Seop MOON ; Gwang Ha KIM ; Su Jin HONG ; Hyuk Soon CHOI
Gut and Liver 2024;18(2):257-264
Background/Aims:
Tegoprazan is a novel potassium-competitive acid blocker that has beneficial effects on acid-related disorders such as gastroesophageal reflux and peptic ulcer diseases.This study aimed to validate the effect of tegoprazan on endoscopic submucosal dissection (ESD)-induced artificial ulcers.
Methods:
Patients from 16 centers in Korea who underwent ESD for gastric neoplasia were enrolled. After ESD, pantoprazole was administered intravenously for 48 hours. The patients were randomly allocated to either the tegoprazan or esomeprazole group. Tegoprazan 50 mg or esomeprazole 40 mg were administered for 4 weeks, after which gastroscopic evaluation was performed. If the artificial ulcer had not healed, the same dose of tegoprazan or esomeprazole was administered for an additional 4 weeks, and a gastroscopic evaluation was performed.
Results:
One hundred sixty patients were enrolled in this study. The healing rates of artificial ulcers at 4 weeks were 30.3% (23/76) and 22.1% (15/68) in the tegoprazan and esomeprazole groups, respectively (p=0.006). At 8 weeks after ESD, the cumulative ulcer healing rates were 73.7% (56/76) and 77.9% (53/68) in the tegoprazan and esomeprazole groups, respectively (p=0.210). Delayed bleeding occurred in two patients in the tegoprazan group (2.6%) and in one patient in the esomeprazole group (1.5%). Other adverse events were negligible in both groups.
Conclusions
Tegoprazan showed similar effects on post-ESD artificial ulcer healing in comparison with esomeprazole.
4.3-Deoxysappanchalcone Inhibits Cell Growth of Gefitinib-Resistant Lung Cancer Cells by Simultaneous Targeting of EGFR and MET Kinases
Jin-Young LEE ; Seung-On LEE ; Ah-Won KWAK ; Seon-Bin CHAE ; Seung-Sik CHO ; Goo YOON ; Ki-Taek KIM ; Yung Hyun CHOI ; Mee-Hyun LEE ; Sang Hoon JOO ; Jin Woo PARK ; Jung-Hyun SHIM
Biomolecules & Therapeutics 2023;31(4):446-455
The mechanistic functions of 3-deoxysappanchalcone (3-DSC), a chalcone compound known to have many pharmacological effects on lung cancer, have not yet been elucidated. In this study, we identified the comprehensive anti-cancer mechanism of 3-DSC, which targets EGFR and MET kinase in drug-resistant lung cancer cells. 3-DSC directly targets both EGFR and MET, thereby inhibiting the growth of drug-resistant lung cancer cells. Mechanistically, 3-DSC induced cell cycle arrest by modulating cell cycle regulatory proteins, including cyclin B1, cdc2, and p27. In addition, concomitant EGFR downstream signaling proteins such as MET, AKT, and ERK were affected by 3-DSC and contributed to the inhibition of cancer cell growth. Furthermore, our results show that 3-DSC increased redox homeostasis disruption, ER stress, mitochondrial depolarization, and caspase activation in gefitinib-resistant lung cancer cells, thereby abrogating cancer cell growth. 3-DSC induced apoptotic cell death which is regulated by Mcl-1, Bax, Apaf-1, and PARP in gefitinib-resistant lung cancer cells. 3-DSC also initiated the activation of caspases, and the pan-caspase inhibitor, Z-VAD-FMK, abrogated 3-DSC induced-apoptosis in lung cancer cells. These data imply that 3-DSC mainly increased mitochondria-associated intrinsic apoptosis in lung cancer cells to reduce lung cancer cell growth. Overall, 3-DSC inhibited the growth of drug-resistant lung cancer cells by simultaneously targeting EGFR and MET, which exerted anti-cancer effects through cell cycle arrest, mitochondrial homeostasis collapse, and increased ROS generation, eventually triggering anticancer mechanisms. 3-DSC could potentially be used as an effective anti-cancer strategy to overcome EGFR and MET target drug-resistant lung cancer.
5.Clinical practice guidelines for percutaneous endoscopic gastrostomy
Chung Hyun TAE ; Ju Yup LEE ; Moon Kyung JOO ; Chan Hyuk PARK ; Eun Jeong GONG ; Cheol Min SHIN ; Hyun LIM ; Hyuk Soon CHOI ; Miyoung CHOI ; Sang Hoon KIM ; Chul-Hyun LIM ; Jeong-Sik BYEON ; Ki-Nam SHIM ; Geun Am SONG ; Moon Sung LEE ; Jong-Jae PARK ; Oh Young LEE ;
Clinical Endoscopy 2023;56(4):391-408
With an aging population, the number of patients with difficulty in swallowing due to medical conditions is gradually increasing. In such cases, enteral nutrition is administered through a temporary nasogastric tube. However, the long-term use of a nasogastric tube leads to various complications and a decreased quality of life. Percutaneous endoscopic gastrostomy (PEG) is the percutaneous placement of a tube into the stomach that is aided endoscopically and may be an alternative to a nasogastric tube when enteral nutritional is required for four weeks or more. This paper is the first Korean clinical guideline for PEG developed jointly by the Korean College of Helicobacter and Upper Gastrointestinal Research and led by the Korean Society of Gastrointestinal Endoscopy. These guidelines aimed to provide physicians, including endoscopists, with the indications, use of prophylactic antibiotics, timing of enteric nutrition, tube placement methods, complications, replacement, and tube removal for PEG based on the currently available clinical evidence.
6.Clinical Practice Guideline for Percutaneous Endoscopic Gastrostomy
Chung Hyun TAE ; Ju Yup LEE ; Moon Kyung JOO ; Chan Hyuk PARK ; Eun Jeong GONG ; Cheol Min SHIN ; Hyun LIM ; Hyuk Soon CHOI ; Miyoung CHOI ; Sang Hoon KIM ; Chul-Hyun LIM ; Jeong-Sik BYEON ; Ki-Nam SHIM ; Geun Am SONG ; Moon Sung LEE ; Jong-Jae PARK ; Oh Young LEE ;
The Korean Journal of Gastroenterology 2023;82(3):107-121
With an aging population, the number of patients with difficulty in swallowing due to medical conditions is gradually increasing. In such cases, enteral nutrition is administered through a temporary nasogastric tube. However, the long-term use of a nasogastric tube leads to various complications and a decreased quality of life. Percutaneous endoscopic gastrostomy (PEG) is the percutaneous placement of a tube into the stomach that is aided endoscopically and may be an alternative to a nasogastric tube when enteral nutritional is required for four weeks or more. This paper is the first Korean clinical guideline for PEG developed jointly by the Korean College of Helicobacter and Upper Gastrointestinal Research and led by the Korean Society of Gastrointestinal Endoscopy. These guidelines aimed to provide physicians, including endoscopists, with the indications, use of prophylactic antibiotics, timing of enteric nutrition, tube placement methods, complications, replacement, and tubes removal for PEG based on the currently available clinical evidence.
7.Breast Tissue Reconstruction Using Polycaprolactone Ball Scaffolds in a Partial Mastectomy Pig Model
Kyu-Sik SHIM ; Da Hye RYU ; Han-Saem JO ; Ki-Bum KIM ; Do-Hyun KIM ; Yong-Kyu PARK ; Min HEO ; Hee-Eun CHO ; Eul-Sik YOON ; Won Jai LEE ; Tai Suk ROH ; Seung Yong SONG ; Wooyeol BAEK
Tissue Engineering and Regenerative Medicine 2023;20(4):607-619
BACKGROUND:
Breast cancer patients suffer from lowered quality of life (QoL) after surgery. Breast conservancy surgery (BCS) such as partial mastectomy is being practiced and studied as an alternative to solve this problem. This study confirmed breast tissue reconstruction in a pig model by fabricating a 3-dimensional (3D) printed Polycaprolactone spherical scaffold (PCL ball) to fit the tissue resected after partial mastectomy.
METHODS:
A 3D printed Polycaprolactone spherical scaffold with a structure that can help adipose tissue regeneration was produced using computer-aided design (CAD). A physical property test was conducted for optimization. In order to enhance biocompatibility, collagen coating was applied and a comparative study was conducted for 3 months in a partial mastectomy pig model.
RESULTS:
In order to identify adipose tissue and fibroglandular tissue, which mainly constitute breast tissue, the degree of adipose tissue and collagen regeneration was confirmed in a pig model after 3 months. As a result, it was confirmed that a lot of adipose tissue was regenerated in the PCL ball, whereas more collagen was regenerated in the collagen-coated Polycaprolactone spherical scaffold (PCL–COL ball). In addition, as a result of confirming the expression levels of TNF-a and IL-6, it was confirmed that PCL ball showed higher levels than PCL–COL ball.
CONCLUSION
Through this study, we were able to confirm the regeneration of adipose tissue through a 3-dimensional structure in a pig model. Studies were conducted on medium and large-sized animal models for the final purpose of clinical use and reconstruction of human breast tissue, and the possibility was confirmed.
8.Erratum: Correction of Affiliations in the Article “Clinical Characteristics and Treatment Outcomes in Children, Adolescents, and Young-adults with Hodgkin's Lymphoma: a KPHOG Lymphoma Working-party, Multicenter, Retrospective Study”
Jae Min LEE ; Jung Yoon CHOI ; Kyung Taek HONG ; Hyoung Jin KANG ; Hee Young SHIN ; Hee Jo BAEK ; Hoon KOOK ; Seongkoo KIM ; Jae Wook LEE ; Nack-Gyun CHUNG ; Bin CHO ; Seok-Goo CHO ; Kyung Mi PARK ; Eu Jeen YANG ; Young Tak LIM ; Jin Kyung SUH ; Sung Han KANG ; Hyery KIM ; Kyung-Nam KOH ; Ho Joon IM ; Jong Jin SEO ; Hee Won CHO ; Hee Young JU ; Ji Won LEE ; Keon Hee YOO ; Ki Woong SUNG ; Hong Hoe KOO ; Kyung Duk PARK ; Jeong Ok HAH ; Min Kyoung KIM ; Jung Woo HAN ; Seung Min HAHN ; Chuhl Joo LYU ; Ye Jee SHIM ; Heung Sik KIM ; Young Rok DO ; Jae Won YOO ; Yeon Jung LIM ; In-Sang JEON ; Hee won CHUEH ; Sung Yong OH ; Hyoung Soo CHOI ; Jun Eun PARK ; Jun Ah LEE ; Hyeon Jin PARK ; Byung-Kiu PARK ; Soon Ki KIM ; Jae Young LIM ; Eun Sil PARK ; Sang Kyu PARK ; Eun Jin CHOI ; Young Bae CHOI ; Jong Hyung YOON ;
Journal of Korean Medical Science 2021;36(4):e37-
9.Epidemiological Study of Hereditary Hemolytic Anemia in the Korean Pediatric Population during 1997–2016: a Nationwide Retrospective Cohort Study
Ye Jee SHIM ; Hye Lim JUNG ; Hee Young SHIN ; Hyoung Jin KANG ; Jung Yoon CHOI ; Jeong Ok HAH ; Jae Min LEE ; Young Tak LIM ; Eu Jeen YANG ; Hee Jo BAEK ; Hyoung Soo CHOI ; Keon Hee YOO ; Jun Eun PARK ; Seongkoo KIM ; Ji Yoon KIM ; Eun Sil PARK ; Ho Joon IM ; Hee Won CHUEH ; Soon Ki KIM ; Jae Hee LEE ; Eun Sun YOO ; Hyeon Jin PARK ; Jun Ah LEE ; Meerim PARK ; Hyun Sik KANG ; Ji Kyoung PARK ; Na Hee LEE ; Sang Kyu PARK ; Young-Ho LEE ; Seong Wook LEE ; Eun Jin CHOI ; Seom Gim KONG
Journal of Korean Medical Science 2020;35(33):e279-
Background:
Hereditary hemolytic anemia (HHA) is a rare disease characterized by premature red blood cell (RBC) destruction due to intrinsic RBC defects. The RBC Disorder Working Party of the Korean Society of Hematology established and updated the standard operating procedure for making an accurate diagnosis of HHA since 2007. The aim of this study was to investigate a nationwide epidemiology of Korean HHA.
Methods:
We collected the data of a newly diagnosed pediatric HHA cohort (2007–2016) and compared this cohort's characteristics with those of a previously surveyed pediatric HHA cohort (1997–2006) in Korea. Each participant's information was retrospectively collected by a questionnaire survey.
Results:
A total of 369 children with HHA from 38 hospitals distributed in 16 of 17 districts of Korea were investigated. RBC membranopathies, hemoglobinopathies, RBC enzymopathies, and unknown etiologies accounted for 263 (71.3%), 59 (16.0%), 23 (6.2%), and 24 (6.5%) of the cases, respectively. Compared to the cohort from the previous decade, the proportions of hemoglobinopathies and RBC enzymopathies significantly increased (P < 0.001 and P = 0.008, respectively). Twenty-three of the 59 hemoglobinopathy patients had immigrant mothers, mostly from South-East Asia.
Conclusion
In Korea, thalassemia traits have increased over the past 10 years, reflecting both increased awareness of this disease and increased international marriages. The enhanced recognition of RBC enzymopathies is due to advances in diagnostic technique; however, 6.5% of HHA patients still do not have a clear diagnosis. It is necessary to improve accessibility of diagnosing HHA.
10.Clinical Characteristics and Treatment Outcomes in Children, Adolescents, and Young-adults with Hodgkin's Lymphoma:a KPHOG Lymphoma Working-party, Multicenter, Retrospective Study
Jae Min LEE ; Jung Yoon CHOI ; Kyung Taek HONG ; Hyoung Jin KANG ; Hee Young SHIN ; Hee Jo BAEK ; Seongkoo KIM ; Jae Wook LEE ; Nack-Gyun CHUNG ; Bin CHO ; Seok-Goo CHO ; Kyung Mi PARK ; Eu Jeen YANG ; Young Tak LIM ; Jin Kyung SUH ; Sung Han KANG ; Hyery KIM ; Kyung-Nam KOH ; Ho Joon IM ; Jong Jin SEO ; Hee Won CHO ; Hee Young JU ; Ji Won LEE ; Keon Hee YOO ; Ki Woong SUNG ; Hong Hoe KOO ; Kyung Duk PARK ; Jeong Ok HAH ; Min Kyoung KIM ; Jung Woo HAN ; Seung Min HAHN ; Chuhl Joo LYU ; Ye Jee SHIM ; Heung Sik KIM ; Young Rok DO ; Jae Won YOO ; Yeon Jung LIM ; In-Sang JEON ; Hee won CHUEH ; Sung Yong OH ; Hyoung Soo CHOI ; Jun Eun PARK ; Jun Ah LEE ; Hyeon Jin PARK ; Byung-Kiu PARK ; Soon Ki KIM ; Jae Young LIM ; Eun Sil PARK ; Sang Kyu PARK ; Eun Jin CHOI ; Young Bae CHOI ; Jong Hyung YOON ; Hoon KOOK ;
Journal of Korean Medical Science 2020;35(46):e393-
Background:
Hodgkin's lymphoma (HL) constitutes 10%–20% of all malignant lymphomas and has a high cure rate (5-year survival, around 90%). Recently, interest has increased concerning preventing secondary complications (secondary cancer, endocrine disorders) in long-term survivors. We aimed to study the epidemiologic features and therapeutic outcomes of HL in children, adolescents, and young adults in Korea.
Methods:
We performed a multicenter, retrospective study of 224 patients aged < 25 years diagnosed with HL at 22 participating institutes in Korea from January 2007 to August 2016.
Results:
A higher percentage of males was diagnosed at a younger age. Nodular sclerosis histopathological HL subtype was most common, followed by mixed cellularity subtype.Eighty-one (36.2%), 101 (45.1%), and 42 (18.8%) patients were classified into low, intermediate, and high-risk groups, respectively. Doxorubicin, bleomycin, vinblastine, dacarbazine was the most common protocol (n = 102, 45.5%). Event-free survival rate was 86.0% ± 2.4%, while five-year overall survival (OS) rate was 96.1% ± 1.4%: 98.7% ± 1.3%, 97.7% ± 1.6%, and 86.5% ± 5.6% in the low, intermediate, and high-risk groups, respectively (P = 0.021). Five-year OS was worse in patients with B-symptoms, stage IV disease, highrisk, splenic involvement, extra-nodal lymphoma, and elevated lactate dehydrogenase level.In multivariate analysis, B-symptoms and extra-nodal involvement were prognostic factors for poor OS. Late complications of endocrine disorders and secondary malignancy were observed in 17 and 6 patients, respectively.
Conclusion
This is the first study on the epidemiology and treatment outcomes of HL in children, adolescents, and young adults in Korea. Future prospective studies are indicated to develop therapies that minimize treatment toxicity while maximizing cure rates in children, adolescents, and young adults with HL.

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