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Kim, Jina,Song, Jaeyoung,Ji, Hyun Dong,Yoo, Eun Kyung,Lee, Jae-Eon,Lee, Sang Bong,Oh, Ji Min,Lee, Seungmi,Hwang, Ji Sun,Yoon, Heeseok,Kim, Dong-Su,Lee, Su-Jeong,Jeong, Minseon,Lee, Sungwoo,Kim, Kyung- American Chemical Society 2019 Journal of medicinal chemistry Vol.62 No.4
<P>An inverse agonist of estrogen-related receptor-γ (ERRγ), an orphan nuclear receptor encoded by E<I>srrg</I>, enhances sodium iodide symporter-mediated radioiodine uptake in anaplastic thyroid cancer (ATC) cells, thereby facilitating responsiveness to radioiodine therapy in vitro. We synthesized potent, selective, and orally bioavailable ERRγ-inverse agonists and evaluated their activity by analyzing in vitro pharmacology and absorption, distribution, metabolism, excretion, and toxicity profiles. X-ray crystallographic analysis of the ligand and ERRγ complex showed that <B>35</B> completely binds to the target protein (PDB 6A6K). Our results showed improved radioiodine avidity in ATC cells through compound <B>35</B>-mediated upregulation of iodide-handling genes, leading to enhanced responsiveness to radioiodine therapy in vitro. Importantly, in vivo <SUP>124</SUP>I-positron emission tomography/computed tomography imaging revealed that <B>35</B> increases radioiodine avidity in CAL62 tumors. Collectively, these results demonstrated that <B>35</B> can be developed as a promising treatment for ERRγ-related cancer in the future.</P> [FIG OMISSION]</BR>
Lee, Dong Hwan,Lim, Jeong-A,Lee, Juneok,Roh, Eunjung,Jung, Kyusuk,Choi, Minseon,Oh, Changsik,Ryu, Sangryeol,Yun, Jongchul,Heu, Sunggi Society for General Microbiology 2013 Microbiology Vol.159 No.7
<P><I>Pectobacterium carotovorum</I> subsp. <I>carotovorum</I> is a well-known plant pathogen that causes severe soft rot disease in various crops, resulting in considerable economic loss. To identify pathogenicity-related factors, Chinese cabbage was inoculated with 5314 transposon mutants of <I>P. carotovorum</I> subsp. <I>carotovorum</I> Pcc21 derived using Tn5 transposon mutagenesis. A total of 35 reduced-virulence or avirulent mutants were isolated, and 14 loci were identified. The 14 loci could be functionally grouped into nutrient utilization (<I>pyrD</I>, <I>purH</I>, <I>purD</I>, <I>leuA</I> and <I>serB</I>), production of plant cell-wall-degrading enzymes (PCWDEs) (<I>expI</I>, <I>expR</I> and PCC21_023220), motility (<I>flgA, fliA</I> and <I>flhB</I>), biofilm formation (<I>expI</I>, <I>expR</I> and <I>qseC</I>), susceptibility to antibacterial plant chemicals (<I>tolC</I>) and unknown function (ECA2640). Among the 14 genes identified, <I>qseC</I>, <I>tolC</I> and PCC21_023220 are novel pathogenicity factors of <I>P. carotovorum</I> subsp. <I>carotovorum</I> involved in biofilm formation, phytochemical resistance and PCWDE production, respectively.</P>
Minseon LEE,Soonjo KWON 한국생물공학회 2021 한국생물공학회 학술대회 Vol.2021 No.10
Natural killer (NK) cells are responsible for the effector function against tumors in innate immune system, predominantly mediated by the secretion of lytic granules containing granzyme and perforin at immunological synapses. However, strategies for NK cell-immunotherapy still should be developed due to the existing immune evasion of tumors by protecting cells from granule uptake and being resistant to NK cell-mediated killing. In this study, we designed a direct current electrical stimulation (ES) system using platinum electrodes as a strategy for enhancing cytotoxic activity and half-life of NK cells for efficient immunotherapy. ES effects have been studied in tissue engineering for bone healing and stem cells by targeting calcium signaling on cell differentiation and migration. Exposure to electrical field could induce changes in calcium flux and mediated pathway, which could be also indispensable for exocytosis of cytotoxic enzyme and tumor killing in NK cells. Cultured KHYG-1 cells were exposed to 1hr direct current ES (voltage range from 0.2 to 1.0V/㎝) and effect of stimulation was analyzed by cell viability, NK cell-mediated cytotoxicity, and gene expression level of related genes. Gene expression level of GZMB was 1.36-fold and 1.58-fold higher without any effects on cell viability, following exposure to ES with 0.5V/cm and 1.0V/㎝, respectively. These findings provide the useful insight regarding the strategies for improving NK cell-mediated cytotoxicity through calcium-dependent exocytosis of lytic granules without any genetic modification, which need to be further studied as one of the new immunotherapy methods.