Kh Jung
Asan Medical Center
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Featured researches published by Kh Jung.
PLOS ONE | 2012
Young S. Na; Soo-Jin Yang; Seung Mi Kim; Kh Jung; Jai-Hee Moon; Jae-Sik Shin; Dok Hyun Yoon; Yong Sang Hong; Min-Hee Ryu; Jae Lyun Lee; Jung Shin Lee; Tae Won Kim
YM155, which inhibits the anti-apoptotic protein survivin, is known to exert anti-tumor effects in various cancers, including prostate and lung cancer. However, there are few reports describing the inhibitory effect of YM155 on human pancreatic cancers that highly express survivin. Here, we tested the effects of YM155 on a variety of cancer cell lines, including pancreatic cancer cells. We found that YM155 exerts an anti-proliferative effect in pancreatic cancer cells, inducing cell death through suppression of XIAP (X-linked inhibitor of apoptosis) as well as survivin without affecting the anti-apoptotic proteins Bcl-xL or Mcl-1. YM155 also inhibited tumor growth in vivo, reducing the size of pancreatic cancer cell line MIAPaCa-2 xenografts by 77.1% on day 31. Western blot analyses further showed that YM155 downregulated phosphoinoside 3-kinase (PI3K) expression and reduced the levels of phosphorylated (activated) extracellular signal-regulated kinase (ERK) and STAT3 (signal transducer and activator of transcription 3) in PANC-1 cells. Interestingly, we also found that YM155 downregulated the epidermal growth factor receptor (EGFR) in various cancer cell lines and induced the EGFR phosphorylation and ubiquitination of EGFR in PANC-1 cells. YM155 also modestly promoted the ubiquitination of survivin and XIAP. Therefore, YM155 acts through modulation of EGFR and survivin expression to subsequently reduce survival. We suggest that YM155 has potential as a therapeutic agent in the treatment of pancreatic cancer.
Cancer Chemotherapy and Pharmacology | 2011
Young-Soon Na; Kh Jung; Seung-Mi Kim; Yong Sang Hong; Min-Hee Ryu; Se Jin Jang; Dae Hyuk Moon; Dong-Hyung Cho; Jin Cheon Kim; Jung Shin Lee; Tae Won Kim
PurposeHistone deacetylase inhibitors (HDACIs), such as PXD101 and suberoylanilide hydroxamic acid, inhibit proliferation and stimulate apoptosis of tumor cells. The enhanced effectiveness of chemotherapy or radiotherapy when combined with HDACIs has been observed in several cancers. In this study, we investigated the antitumor effect of PXD101 combined with irinotecan in colon cancer.MethodsHCT116 and HT29 colon cancer cells for cell viability assay were treated with PXD101 and/or SN-38, the active form of irinotecan. Antitumor effects of HCT116 and HT29 xenografts treated with these combinations were evaluated. [18F]FLT-PET was used to detect early responses to PXD101 and irinotecan in colon cancer.ResultsPXD101 and SN38 possessed dose-dependent antiproliferative activity against HCT116 and HT29 cells and exerted a synergistic effect when used in combination. In xenografted mice, PXD101 in combination with irinotecan dramatically inhibited tumor growth without causing additive toxicity. Apoptotic effects on xenograft tumors were greater with combined treatment than with irinotecan alone. [18F]FLT-PET imaging revealed a 64% decrease in [18F]FLT uptake in tumors of HCT116 xenograft-bearing mice treated with a combination of PXD101 and irinotecan, indicating a decrease in thymidine kinase 1 (TK1) activity. These results were supported by Western blot analyses showing a decrease in tumor thymidine kinase 1 protein levels, suggesting that [18F]FLT-PET can be used to non-invasively detect early responses to these agents.ConclusionsThese data show that PXD101 increases the cytotoxic activity of irinotecan in in vitro and in vivo colon cancer models and suggest these agent combinations should be explored in the treatment of colon cancer.
Journal of Biological Chemistry | 2012
Seungwoo Hong; Dong-Hoon Jin; Jae-Sik Shin; Jai-Hee Moon; Young-Soon Na; Kh Jung; Seung-Mi Kim; Jin Cheon Kim; Kyu-pyo Kim; Yong Sang Hong; Eun Kyung Choi; Jung Shin Lee; Tae Won Kim
Background: BRAF is a downstream effector kinase of Ras. Results: RNF149, a RING finger domain-containing E3 ubiquitin ligase, is one of the several proteins shown to interact with wild-type BRAF by tandem affinity purification. Conclusion: RNF149 induces ubiquitination and subsequent proteasomal degradation of wild-type but not mutant BRAF. Significance: This is the first ubiquitin ligase shown to degrade wild-type BRAF in a proteasome-dependent manner. Members of the RAF family (ARAF, BRAF, and CRAF/RAF-1) are involved in a variety of cellular activities, including growth, survival, differentiation, and transformation. An oncogene encodes BRAF, the function of which is linked to MEK activation. BRAF is the most effective RAF kinase in terms of induction of MEK/ERK activity. However, the mechanisms involved in BRAF regulation remain unclear. In the present work, we used a tandem affinity purification approach to show that RNF149 (RING finger protein 149) interacts with wild-type BRAF. The latter protein is a RING domain-containing E3 ubiquitin ligase involved in control of gene transcription, translation, cytoskeletal organization, cell adhesion, and epithelial development. We showed that RNF149 bound directly to the C-terminal kinase-containing domain of wild-type BRAF and induced ubiquitination, followed by proteasome-dependent degradation, of the latter protein. Functionally, RNF149 attenuated the increase in cell growth induced by wild-type BRAF. However, RNF149 did not bind to mutant BRAF or induce ubiquitination thereof. Thus, we show that RNF149 is an E3 ubiquitin ligase active on wild-type BRAF.
Scientific Reports | 2018
Ji Ye Kwon; Seung Hoon Lee; Hyun-Sik Na; Kh Jung; JeongWon Choi; Keun Hyung Cho; Chang-Yong Lee; Seok Jung Kim; Sung-Hwan Park; Dongyun Shin; Mi-La Cho
Osteoarthritis (OA) is a major degenerative joint condition that causes articular cartilage destruction. It was recently found that enhancement of chondroclasts and suppression in Treg cell differentiation are involved in the pathogenesis of OA. Kartogenin (KGN) is a small drug-like molecule that induces chondrogenesis in mesenchymal stem cells (MSCs). This study aimed to identify whether KGN can enhance severe pain behavior and improve cartilage repair in OA rat model. Induction of OA model was loaded by IA-injection of MIA. In the OA rat model, treatment an intra-articular injection of KGN. Pain levels were evaluated by analyzing PWL and PWT response in animals. Histological analysis and micro-CT images of femurs were used to analyze cartilage destruction. Gene expression was measured by real-time PCR. Immunohistochemistry was analyzed to detect protein expression. KGN injection significantly decreased pain severity and joint destruction in the MIA-induced OA model. KGN also increased mRNA levels of the anti-inflammatory cytokine IL-10 in OA patients’ chondrocytes stimulated by IL-1β. Decreased chondroclast expression, and increased Treg cell expression. KGN revealed therapeutic activity with the potential to reduce pain and improve cartilage destruction. Thus, KGN could be a therapeutic molecule for OA that inhibits cartilage damage.
Immunology Letters | 2018
Seung Hoon Lee; Ji Ye Kwon; Joo-Yeon Jhun; Kh Jung; Sung-Hwan Park; Chul Woo Yang; YongSin Cho; Seok Jung Kim; Mi-La Cho
Osteoarthritis (OA) is a chronic and degenerative disease that causes pain, cartilage deformation, and joint inflammation. Lactobacillus species have been used as dietary supplements to induce the production of antimicrobial and anti-inflammatory factors. The goal of this study was to determine whether Lactobacillus acidophilus ameliorates monosodium iodoacetate-induced OA. L. acidophilus showed anti-nociceptive properties and protected against cartilage destruction. It also downregulated the levels of proinflammatory cytokines and increased the levels of anti-inflammatory cytokines in the joints of OA rats. L. acidophilus additionally restored the balance between anabolic and catabolic factors in chondrocytes from OA patients. These results suggest that L. acidophilus can alleviate OA-associated pain and delay the progression of the disease by inhibiting proinflammatory cytokine production and reducing cartilage damage.
Immunology Letters | 2018
Seung Hoon Lee; Hye-Rim Lee; Ji Ye Kwon; Kh Jung; Se-Young Kim; Keun-Hyung Cho; JeongWon Choi; Han Hee Lee; Bo-In Lee; Dae-Myung Jue; Mi-La Cho
A20 is a zinc finger protein that effectively inhibits the activation of nuclear factor (NF)-κB to downregulate the expression of tumor necrosis factor-α, interleukin (IL)-1β, and IL-17. A20 also plays a crucial role as a feedback inhibitor of the inflammatory response. Due to its inhibitory role, A20 may be useful in regulating diseases resulting from chronic inflammation and excessive pro-inflammatory cytokine production, such as colitis. Patients with colitis produce high levels of pro-inflammatory cytokines in the intestine. Therefore, this study aimed to investigate whether A20 improves experimental colitis by reducing high levels of inflammation in the intestine. An A20 overexpression vector was administered to mice by intrarectal injection after colitis induction. Histological analysis by immunohistochemistry was used to score sections of the intestine. Confocal laser scanning microscopy was used to identify the expression of IL-17 and forkhead box p (FOXP) 3 protein in spleen tissues. Protein expression induced by STAT3 and NF-κB signaling was analyzed by western blot. We found that A20 reduced the colitis activity index score and the histological score of the intestine. A20 also decreased inflammatory cytokine levels in the intestine and increased colon length. Additionally, A20 overexpression downregulated the activation of NF-kB and STAT3. A20 also reduced IL-17 expression in CD4+ T cells from spleen sections. In contrast, A20 overexpression enhanced the expression of FOXP3 in CD4+ T cells. These results suggest that A20 may inhibit the progression of colitis by decreasing inflammation via inhibition of NF-κB, phosphorylated STAT3, and IL-17.
Frontiers in Immunology | 2018
Da Som Kim; Jeong-Eun Kwon; Seung Hoon Lee; Eun-Kyung Kim; Jun-Geol Ryu; Kh Jung; JeongWon Choi; Min-Jung Park; Young-Mee Moon; Sung-Hwan Park; Mi-La Cho; Seung-Ki Kwok
Rheumatoid arthritis (RA) is a systemic autoimmune disease caused by both genetic and environmental factors. Recently, investigators have focused on the gut microbiota, which is thought to be an environmental factor that affects the development of RA. Metabolites secreted by the gut microbiota maintain homeostasis in the gut through various mechanisms [e.g., butyrate, which is one of the major metabolites of gut microbiota, exerts an anti-inflammatory effect by activating G-protein-coupled receptors and inhibiting histone deacetylases (HDACs)]. Here, we focused on the inhibition of the HDACs by butyrate in RA. To this end, we evaluated the therapeutic effects of butyrate in an animal model of autoimmune arthritis. The arthritis score and incidence were lower in the butyrate-treated group compared to the control group. Also, butyrate inhibited HDAC2 in osteoclasts and HDAC8 in T cells, leading to the acetylation of glucocorticoid receptors and estrogen-related receptors α, respectively. Additionally, control of the TH17/Treg cell balance and inhibition of osteoclastogenesis were confirmed by the changes in target gene expression. Interleukin-10 (IL-10) produced by butyrate-induced expanded Treg cells was critical, as treatment with butyrate did not affect inflammatory arthritis in IL-10-knockout mice. This immune-cell regulation of butyrate was also detected in humans. These findings suggest that butyrate is a candidate agent for the treatment of RA.
PLOS ONE | 2017
Joo-Yeon Jhun; Jeong-Eun Kwon; Se-Young Kim; Jeong-Hee Jeong; Hyun Sik Na; Eun-Kyung Kim; Seung Hoon Lee; Kh Jung; Jun-Ki Min; Mi-La Cho; Yeonseok Chung
Atherosclerosis is a chronic inflammatory disease caused by the accumulation of excess lipid in the aorta and the severity is regulated by T lymphocytes subsets. Rebamipide has therapeutic activity in collagen induced arthritis (CIA) by controlling the balance between T helper (Th) 17 and regulatory T (Treg) cells. In this study, we aimed to determine whether rebamipide reduces the development of atherosclerosis. To investigate the therapeutic effect of rebamipide, ApoE-KO mice fed a western diet were administered rebamipide orally for 8 weeks. Mice were sacrificed followed by the evaluation of plaque formation in the aorta or immunohistochemistry for IL-17 and Foxp3. Serum was also prepared to determine the pro-inflammatory cytokine levels. The ability of rebamipide to regulate lipid metabolism or inflammation was confirmed ex vivo. Results The oral administration of rebamipide decreased plaque formation in atherosclerotic lesions as well as the markers of metabolic disorder in ApoE-deficient mice with atherosclerosis. Pro-inflammatory cytokines were also suppressed by rebamapide. In addition, the population of Th17 was decreased, whereas Treg was increased in the spleen of rebamipide-treated ApoE deficient mice. Rebamipide also ameliorated the severity of obese arthritis and has the capability to reduce the development of atherosclerosis by controlling the balance between Th17 and Treg cells. Thus, rebamipide could be a therapeutic agent to improve the progression of inflammation in metabolic diseases.
Cancer Research | 2017
Kh Park; M. Woo; Je Kim; J-H Ahn; Kh Jung; S-B Kim
Background: Prior technique to measure cell free DNA(CFD) is labor-intensive and expensive, while, recently developed fluorescent CFD assay is more simple and convenient.The aim of this study was to evaluate the role of CFD measured by a fluorescent assay as a biomarker of patients with triple negative breast cancer (TNBC) received neoadjuvant chemotherapy Methods: We prospectively enrolled patients with TNBC, clinical stage II or III (T>1.5cm or lymph node > 1.5cm), who were scheduled for neoadjuvant chemotherapy. Patients received 4 cycles of adriamycin 60 mg/m2 plus cyclophosphamide 600 mg/m2 (AC) followed by 4 cycles of cisplatin or docetaxel, and surgery. Plasma samples were obtained from patients before initial chemotherapy (baseline-CFD) and after 4 cycles of AC neoadjuvant chemotherapy (AC-CFD). Results: This study included 72 patients who met the inclusion criteria. The mean levels of baseline-CFD and AC-CFD were 239±68 ng/mL and 210±66 ng/mL, respectively, and the CFD level was significantly decreased after AC chemotherapy.( p=0.001) The baseline-CFD was not associated with initial tumor characteristics. (T stage 1-2 vs. 3, p=0.313; N stage 0 vs. 1-3, p=0.317) There was no statistically significant difference between patients with response (CR or PR) to AC chemotherapy and those without response in terms of baseline-CFD, AC-CFD, and change of CFD between two values. (p=0.814, p=0.839, p=0.927) With 33.6 months of median follow up, there were 18 cases of relapse. Relapsed group showed numerically higher level of baseline-CFD, although it was not statistically significant. (relapse, 259 ng/mL; non-relapse, 233 ng/mL; p=0.161) We performed a ROC curve analysis of baseline-CFD for relapse, and found an area under the curve of 0.62 (95% CI, 0.46-0.78) at 222 ng/mL. Patients with baseline-CFD above 222 showed higher relapses than those below 222. (HR, 2.75; 95% CI, 0.96-7.84; p = 0.059) Conclusions: The baseline-CFD obtained using a simple and convenient fluorescent assay could predict relapse, suggesting baseline-CFD as a potential biomarker for risk stratification of TNBC. Citation Format: Park K, Woo M, Kim JE, Ahn J-H, Jung KH, Kim S-B. Circulating cell-free DNA (CFD) measured by a simple fluorescent assay to predict relapse in triple negative breast cancer patients receiving neoadjuvant chemotherapy: A biomarker substudy of prospective observational study (NCT02001519, NCT02001506) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-02-14.
Cancer Research | 2016
T. Kim; Jh Sohn; S-B Kim; Jh Yoon; Gm Kim; K.H. Lee; S-J Koh; Youn-Soo Park; Se Lee; Y Chae; Kwan Sik Lee; Ke Lee; Hs Won; J. Kim; Jong-Hyeon Jeong; Kh Park; Ey Cho; Y-H Im; S-A Im; Kh Jung
Background Recently, many clinical trials (TRIAL) especially incorporated with molecular-targeted agents are being conducted in treatment for breast cancer worldwide. However, the relation of participating clinical trials with survival has not been actively studied. This study was designed to evaluate whether participation in clinical trials could improve overall survival (OS) or not in patients with metastatic breast cancer (MBC), compared with conventional treatment. Method Korean Cancer Study Group (KCSG) has successfully established Nationwide Cohort in KOREA to conduct diachronic analysis (KCSG BR 14-07). Clinical data for patients with MBC were collected from this Cohort. OS was defined as the time duration from first diagnosis of metastasis to any cause of death. This work is supported by National Strategic Coordinating Center for Clinical Research (H110C2020). Results A total of 575 patients with metastatic breast from 26 institutes in KOREA cancer MBC were consequently enrolled between September 2014 and May 2015. 156 (27.1%) of patients were enrolled to at least one or more clinical trials and 419 patients received only conventional treatment (CONV). Age, hormone status, HER2 status, initial pathologic stage, metastasis versus recurrence, adjuvant treatment, ECOG performance status (PS) (0, 1 vs 2 or more) were similar between TRIAL and CONV. 30% of trials were associated with HER2-targeted agents. As initial treatment, chemotherapy was more frequently used in TRIAL (85.9%) than in CONV (79.0%) (P=0.038). Number of regimens of chemotherapy was greater in TRIAL (2.9+/-1.8) than CONV (2.1+/-1.6) (P Conclusion Participating in clinical trials could be associated with prolongation of survival. This results constantly maintained in HER2-positive and triple-negative MBC. These findings suggested that clinical trials are useful for the patients with MBC, even if the patients do not complete the standard treatment. Citation Format: Kim T-Y, Sohn JH, Kim S-B, Yoon JH, Kim GM, Lee KH, Koh S-J, Park YH, Lee SE, Chae Y, Lee KS, Lee KE, Won HS, Kim JH, Jeong J, Park KH, Cho EK, Im Y-H, Im S-A, Jung KH. Does participation in clinical trials influence on survival in patients with metastatic breast cancer?. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-10-03.