Misun Yun
Chonnam National University
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Publication
Featured researches published by Misun Yun.
Angewandte Chemie | 2015
Joong Jae Lee; Hyo Jung Choi; Misun Yun; Yingjin Kang; Ji Eun Jung; Yiseul Ryu; Tae Yoon Kim; Young Je Cha; Hyun Soo Cho; Jung Joon Min; Chul Woong Chung; Hak-Sung Kim
Targeted therapy based on protein-drug conjugates has attracted significant attention owing to its high efficacy and low side effects. However, efficient and stable drug conjugation to a protein binder remains a challenge. Herein, a chemoenzymatic method to generate highly stable and homogenous drug conjugates with high efficiency is presented. The approach comprises the insertion of the CaaX sequence at the C-terminal end of the protein binder, prenylation using farnesyltransferase, and drug conjugation through an oxime ligation reaction. MMAF and an EGFR-specific repebody are used as the antitumor agent and protein binder, respectively. The method enables the precisely controlled synthesis of repebody-drug conjugates with high yield and homogeneity. The utility of this approach is illustrated by the notable stability of the repebody-drug conjugates in human plasma, negligible off-target effects, and a remarkable antitumor activity in vivo. The present method can be widely used for generating highly homogeneous and stable PDCs for targeted therapy.
PLOS ONE | 2013
Kwangsoo Kim; Jae Ho Jeong; Daejin Lim; Yeongjin Hong; Misun Yun; Jung-Joon Min; Sahng-June Kwak; Hyon E. Choy
During the last decade, an increasing number of papers have described the use of various genera of bacteria, including E. coli and S. typhimurium, in the treatment of cancer. This is primarily due to the facts that not only are these bacteria capable of accumulating in the tumor mass, but they can also be engineered to deliver specific therapeutic proteins directly to the tumor site. However, a major obstacle exists in that bacteria because the plasmid carrying the therapeutic gene is not needed for bacterial survival, these plasmids are often lost from the bacteria. Here, we report the development of a balanced-lethal host-vector system based on deletion of the glmS gene in E. coli and S. typhimurium. This system takes advantage of the phenotype of the GlmS− mutant, which undergoes lysis in animal systems that lack the nutrients required for proliferation of the mutant bacteria, D-glucosamine (GlcN) or N-acetyl-D-glucosamine (GlcNAc), components necessary for peptidoglycan synthesis. We demonstrate that plasmids carrying a glmS gene (GlmS+p) complemented the phenotype of the GlmS− mutant, and that GlmS+p was maintained faithfully both in vitro and in an animal system in the absence of selection pressure. This was further verified by bioluminescent signals from GlmS +pLux carried in bacteria that accumulated in grafted tumor tissue in a mouse model. The signal was up to several hundred-fold stronger than that from the control plasmid, pLux, due to faithful maintenance of the plasmid. We believe this system will allow to package a therapeutic gene onto an expression plasmid for bacterial delivery to the tumor site without subsequent loss of plasmid expression as well as to quantify bioluminescent bacteria using in vivo imaging by providing a direct correlation between photon flux and bacterial number.
Journal of Microbiology | 2012
Misun Yun; SangO Pan; Sheng Nan Jiang; Vu H. Nguyen; Seung-Hwan Park; Che-Hun Jung; Hyung-Seok Kim; Jung-Joon Min; Hyon E. Choy; Yeongjin Hong
The use of bacteria has contributed to recent advances in targeted cancer therapy especially for its tumor-specific accumulation and proliferation. In this study, we investigated the molecular events following bacterial therapy using an attenuated Salmonella Typhimurium defective in ppGpp synthesis (ΔppGpp), by analyzing those proteins differentially expressed in tumor tissues from treated and untreated mice. CT26 murine colon cancer cells were implanted in BALB/c mice and allowed to form tumors. The tumor-bearing mice were treated with the attenuated Salmonella Typhimurium. Tumor tissues were analyzed by 2D-PAGE. Fourteen differentially expressed proteins were identified by mass spectrometry. The analysis revealed that cytoskeletal components, including vimentin, drebrin-like protein, and tropomyosin-alpha 3, were decreased while serum proteins related to heme or iron metabolism, including transferrin, hemopexin, and haptoglobin were increased. Subsequent studies revealed that the decrease in cytoskeletal components occurred at the transcriptional level and that the increase in heme and iron metabolism proteins occurred in liver. Most interestingly, the same pattern of increased expression of transferrin, hemopexin, and haptoglobin was observed following radiotherapy at the dosage of 14 Gy.
Molecular Therapy - Oncolytics | 2015
Kwangsoo Kim; Jae Ho Jeong; Daejin Lim; Yeongjin Hong; Hyung-Ju Lim; Geun-Joong Kim; So-ra Shin; Je-Jung Lee; Misun Yun; Robert A. Harris; Jung-Joon Min; Hyon E. Choy
Bacteria can be engineered to deliver anticancer proteins to tumors via a controlled expression system that maximizes the concentration of the therapeutic agent in the tumor. L-asparaginase (L-ASNase), which primarily converts asparagine to aspartate, is an anticancer protein used to treat acute lymphoblastic leukemia. In this study, Salmonellae were engineered to express L-ASNase selectively within tumor tissues using the inducible araBAD promoter system of Escherichia coli. Antitumor efficacy of the engineered bacteria was demonstrated in vivo in solid malignancies. This result demonstrates the merit of bacteria as cancer drug delivery vehicles to administer cancer-starving proteins such as L-ASNase to be effective selectively within the microenvironment of cancer tissue.
Theranostics | 2017
Misun Yun; Dong-Yeon Kim; Joong-jae Lee; Hyeon-Sik Kim; HyungSeok Kim; Ayoung Pyo; Yiseul Ryu; Taeyoon Kim; Jin Hai Zheng; Su Woong Yoo; Hoon Hyun; Gyungseok Oh; Jae-Ho Jeong; Myeongju Moon; Jung-Hyun Min; Seong Young Kwon; Jung Young Kim; Euiheon Chung; Yeongjin Hong; Wan-Sik Lee; Hak-Sung Kim; Jung-Joon Min
The accurate detection of disease-related biomarkers is crucial for the early diagnosis and management of disease in personalized medicine. Here, we present a molecular imaging of human epidermal growth factor receptor (EGFR)-expressing malignant tumors using an EGFR-specific repebody composed of leucine-rich repeat (LRR) modules. The repebody was labeled with either a fluorescent dye or radioisotope, and used for imaging of EGFR-expressing malignant tumors using an optical method and positron emission tomography. Our approach enabled visualization of the status of EGFR expression, allowing quantitative evaluation in whole tumors, which correlated well with the EGFR expression levels in mouse or patients-derived colon cancers. The present approach can be effectively used for the accurate detection of EGFR-expressing cancers, assisting in the development of a tool for detecting other disease biomarkers.
Current Optics and Photonics | 2017
Su Woong Yoo; Hee-Jin Park; Gyungseok Oh; Soonjoo Hwang; Misun Yun; Taejun Wang; Young-Seok Seo; Jung-Joon Min; Ki Hean Kim; Eung-Sam Kim; Young L. Kim; Euiheon Chung
In addition to its typical use for skin rejuvenation, fractional laser irradiation of early cancerous lesions may reduce the risk of tumor development as a byproduct of wound healing in the stroma after the controlled injury. While fractional ablative lasers are commonly used for cosmetic/aesthetic purposes (e.g., photorejuvenation, hair removal, and scar reduction), we propose a novel use of such laser treatments as a stromal treatment to delay tumorigenesis and suppress carcinogenesis. In this study, we found that non-ablative fractional laser (NAFL) irradiation may have a possible suppressive effect on early tumor growth in syngeneic mouse tumor models. We included two syngeneic mouse tumor models in irradiation groups and control groups. In the irradiation group, a thulium fiber based NAFL at 1927 nm was used to irradiate the skin area including the tumor injection region with 70 mJ/spot, while no laser irradiation was applied to the control group. Numerical simulation with the same experimental condition showed that thermal damage was confined only to the irradiation spots, sparing the adjacent tissue area. The irradiation groups of both tumor models showed smaller tumor volumes than the control group at an early tumor growth stage. We also detected elevated inflammatory cytokine levels a day after the NAFL irradiation. NAFL treatment of the stromal tissue could potentially be an alternative anticancer therapeutic modality for early tumorigenesis in a minimally invasive manner.
The Journal of Nuclear Medicine | 2017
Ayoung Pyo; Misun Yun; Hyeon Sik Kim; Taeyoon Kim; Joong-jae Lee; Jung Young Kim; Sunwoo Lee; Seong Young Kwon; Hee-Seung Bom; Hak-Sung Kim; Dong-Yeon Kim; Jung-Joon Min
The epidermal growth factor receptor (EGFR) is a member of the erbB family of receptors and is overexpressed in many tumor types. A repebody is a newly designed nonantibody protein scaffold for tumor targeting that contains leucine-rich repeat modules. In this study, 3 64Cu-labeled anti-EGFR repebodies with different chelators were synthesized, and their biologic characteristics were assessed in cultured cells and tumor-bearing mice. Methods: Repebodies were synthesized with the chelators 2-(p-isothiocyanatobenzyl)-1,4,7-triazacyclononane-N,N′,N,″-triacetic acid trihydrochloride ([p-SCN-Bn]-NOTA), 2,2′,2″-(10-(2-(2,5-dioxopyrrolidin-1-yloxy)-2-oxoethyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl) triacetic acid (DOTA-N-hydroxysuccinimide ester), or 1-(p-isothiocyanatobenzyl)diethylenetriamine pentaacetic acid trihydrochloride ([p-SCN-Bn]-DTPA) in 1.0 M NaHCO3 buffer (pH 9.2) for 24 h. Purified NOTA-, DOTA-, and DTPA-conjugated repebody were radiolabeled with 64Cu in 0.1 M NH4OAc buffer (pH 5.5). To compare the EGFR-binding affinities of the repebodies, cellular uptake studies were performed with the human non–small cell lung cancer cell line H1650 (high expression of EGFR) and the human colon adenocarcinoma cell line SW620 (low expression of EGFR). Biodistribution and small-animal PET imaging studies were performed using H1650 tumor–bearing mice. Results: Radiochemical yields of the 64Cu-labeled repebodies were approximately 70%–80%. Cellular uptake of the NOTA-, DOTA-, and DTPA-repebodies was over 4-fold higher in H1650 cells than in SW620 cells at 1 h. The 3 repebodies had accumulated specifically in H1650 tumor–bearing nude mice by 1 h after intravenous injection and were retained for over 24 h, as measured by the percentage injected dose per gram of tissue (%ID/g). Tumor uptake of all repebodies increased from 1 to 6 h (at 1 h, 6.28, 8.46, and 6.91 %ID/g for NOTA-, DOTA-, and DTPA-repebody, respectively; at 6 h, 9.4, 8.28, and 10.1 %ID/g, respectively). H1650 tumors were clearly visible after injection of each repebody, with high tumor-to-background ratios (at 1 h, 3.43, 4.89, and 2.38 for NOTA-, DOTA-, and DTPA-repebody, respectively; at 6 h, 3.05, 4.36, and 2.08; at 24 h, 3.81, 4.58, and 2.86). Conclusion: The 3 64Cu-repebody complexes demonstrated specific and rapid uptake in EGFR-expressing tumors within 1 h and may have potential as novel EGFR imaging agents for PET.
Bioorganic & Medicinal Chemistry Letters | 2018
Kunal N. More; Jun Young Lee; Dong-Yeon Kim; Nam Chul Cho; Ayoung Pyo; Misun Yun; Hyeon Sik Kim; Hangun Kim; Kwangseok Ko; Jeong-Hoon Park; Dong-Jo Chang
Corrigendum Corrigendum to “Acetazolamide-based [F]-PET tracer: In vivo validation of carbonic anhydrase IX as a sole target for imaging of CA-IX expressing hypoxic solid tumors” [Bioorg. Med. Chem. Lett. 28 (5) (2018) 915–921] Kunal N. More, Jun Young Lee, Dong-Yeon Kim, Nam-Chul Cho, Ayoung Pyo, Misun Yun, Hyeon Sik Kim, Hangun Kim, Kwangseok Ko, Jeong-Hoon Parkb,, Dong-Jo Changa, a College of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University, Suncheon 57922, Republic of Korea b Radiation Instrumentation Research Division, Korea Atomic Energy Research Institute, Jeongeup 56212, Republic of Korea c Department of Nuclear Medicine, Chonam National University, Hwasun Hospital, Hwasun 58128, Republic of Korea d C&C Research Laboratories, DRC, Sungyunkwan University, Suwon 16419, Republic of Korea
Bioorganic & Medicinal Chemistry Letters | 2018
Kunal N. More; Jun Young Lee; Dong-Yeon Kim; Nam Chul Cho; Ayoung Pyo; Misun Yun; Hyeon Sik Kim; Hangun Kim; Kwangseok Ko; Jeong-Hoon Park; Dong-Jo Chang
Carbonic anhydrase IX is overexpressed in many solid tumors including hypoxic tumors and is a potential target for cancer therapy and diagnosis. Reported imaging agents targeting CA-IX are successful mostly in clear cell renal carcinoma as SKRC-52 and no candidate was approved yet in clinical trials for imaging of CA-IX. To validate CA-IX as a valid target for imaging of hypoxic tumor, we designed and synthesized novel [18F]-PET tracer (1) based on acetazolamide which is one of the well-known CA-IX inhibitors and performed imaging study in CA-IX expressing hypoxic tumor model as 4T1 and HT-29 in vivo models other than SKRC-52. [18F]-acetazolamide (1) was found to be insufficient for the specific accumulation in CA-IX expressing tumor. This study might be useful to understand in vivo behavior of acetazolamide PET tracer and can contribute to the development of successful PET imaging agents targeting CA-IX in future. Additional study is needed to understand the mechanism of poor targeting of CA-IX, as if CA-IX is not reliable as a sole target for imaging of CA-IX expressing hypoxic solid tumors.
Journal of Korean Medical Science | 2017
Young Ok Kim; Misun Yun; Jae-Ho Jeong; Seong Min Choi; Seul Kee Kim; Woong Yoon; Chungoo Park; Yeongjin Hong; Young Jong Woo
Progressive cerebellar ataxias are rare diseases during childhood, especially under 6 years of age. In a single family, three affected siblings exhibited Friedreichs-ataxia-like phenotypes before 2 years of age. They had progressive cerebellar atrophy, intellectual disability, and scoliosis. Although their phenotypes were similar to those observed in patients with autosomal recessive cerebellar ataxias, other phenotypes (e.g., seizure, movement disorders, ophthalmologic disturbance, cardiomyopathy, and cutaneous disorders) were not noted in this family. Whole-exome sequencing of the family members revealed one potential heterozygous mutation (c.1209delG, NM_181733.2; p.Met403IlefsX3, NP_859422.2) of the gene encoding conserved oligomeric Golgi complex subunit 5 (COG5). The heterozygous deletion at the fifth base in exon 12 of COG5 caused a frameshift and premature stop. Western blotting of COG5 proteins in the skin tissues from an affected proband showed a significantly decreased level of full length COG5 and smaller, aberrant COG5 proteins. We reported a milder form of COG5 defect showing Friedreichs-ataxia-like phenotypes without hypotonia, microcephaly, and short stature that were observed in most patients with COG5 defect.