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4. Anticancer Activity of Pyrimethamine via Ubiquitin Mediated Degradation of AIMP2-DX2

Author

Kim, Dae Gyu, Park, Chul Min, Huddar, Srigouri, Lim, Semi, Kim, Sunghoon, and Lee, Sunkyung

Subjects
Medicinal and Biomolecular Chemistry, Organic Chemistry, Chemical Sciences, Cancer, Lung, Lung Cancer, Aetiology, 2.1 Biological and endogenous factors, A549 Cells, Amino Acyl-tRNA Synthetases, Animals, Cell Line, Tumor, Exons, Female, Humans, Lung Neoplasms, Mice, Mice, Inbred BALB C, Nuclear Proteins, Pyrimethamine, Ubiquitin, Xenograft Model Antitumor Assays, AIMP2-DX2, anticancer, drug repositioning, pyrimethamine, ubiquitination, Theoretical and Computational Chemistry, Medicinal and biomolecular chemistry, Organic chemistry
Abstract

While aminoacyl-tRNA synthetase-interacting multifunctional protein 2 (AIMP2) is a tumor suppressor, its exon 2-depleted splice variant (AIMP2-DX2 or shortly DX2) is highly expressed in human lung cancer, and the ratio of DX2 to AIMP2 increases according to the progression of lung cancer. In this study, pyrimethamine inhibited the level of DX2 (IC50 = 0.73 µM) in A549 cells expressing nanoluciferase-tagged DX2. In a panel of 5 lung cancer cell lines with various DX2 levels, pyrimethamine most potently suppressed the growth of H460 cells, which express high levels of DX2 (GI50 = 0.01 µM). An immunoblot assay in H460 cells showed that pyrimethamine decreased the DX2 level dose-dependently but did not affect the AIMP2 level. Further experiments confirmed that pyrimethamine resulted in ubiquitination-mediated DX2 degradation. In an in vivo mouse xenograft assay using H460 cells, intraperitoneal administration of pyrimethamine significantly reduced the tumor size and weight, comparable with the effects of taxol, without affecting body weight. Analysis of tumor tissue showed a considerably high concentration of pyrimethamine with a decreased levels of DX2. These results suggest that pyrimethamine, currently used as anti-parasite drug, could be repurposed to treat lung cancer patients expressing high level of DX2.

Published
2020

19. Gracilaria chordasubcritical-water extracts as ameliorant of insulin resistance induced by high-glucose in zebrafish and dexamethasone in L6 myotubes

Author

Thakuri, Laxmi Sen, Park, Chul Min, Park, Jin Woo, and Rhyu, Dong Young

Abstract

Insulin resistance (IR) is a pathological condition in which cells fail to respond normally to insulin. Loss of insulin sensitivity disrupts glucose homeostasis and elevates the risk of developing the metabolic syndrome that includes Type 2 diabetes. This study assesses the effect on subcritical-water extract of Gracilaria chorda(GC) at 210 °C (GCSW210) in IR induction models of high glucose (HG)-induced zebrafish larvae and dexamethasone (DEX)-induced L6 myotubes.

Published
2024
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21. Optimization of 2-Aminoquinazolin-4-(3H)-one Derivatives as Potent Inhibitors of SARS-CoV-2: Improved Synthesis and Pharmacokinetic Properties

Author

Shin, Young Sup, primary, Lee, Jun Young, additional, Jeon, Sangeun, additional, Cho, Jung-Eun, additional, Myung, Subeen, additional, Jang, Min Seong, additional, Kim, Seungtaek, additional, Song, Jong Hwan, additional, Kim, Hyoung Rae, additional, Park, Hyeung-geun, additional, Jeong, Lak Shin, additional, and Park, Chul Min, additional

Published
2022
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23. EPHB2 expression is associated with intestinal phenotype of gastric cancer and indicates better prognosis by suppressing gastric cancer migration

Author

Kim, Hyesung, Myung, Jae Kyung, Paik, Seung Sam, Kim, Hyunsung, Park, Hosub, Kim, Yeon Ju, Lee, Seung Bum, Kim, Heung Up, Song, Hyun Joo, Jeong, In Ho, Hong, Suji, Park, Chul Min, Lee, Cheol, Kim, Younghoon, and Jang, Bogun

Subjects
Original Article
Abstract

The protein tyrosine kinase Ephrin type-B receptor 2 (EPHB2) belongs to one of the intestinal stem cell signature genes and plays a crucial role in maintaining the crypt-villous axis. Herein, we aimed to investigate the expression of EPHB2 during gastric carcinogenesis and evaluated its prognostic and functional significance in gastric cancer (GC). EPHB2 expression was upregulated in intestinal metaplasia and GCs compared to normal antral and fundic glands. EPHB2 mRNA levels were strongly correlated with the intestinal stem cell markers OLFM4, LGR5, and EPHB3. Notably, EPHB2 expression was significantly correlated with CDX2 expression, and in vitro studies demonstrated that CDX2 expression increased both EPHB2 transcription and protein levels. In a large cohort of GC patients, EPHB2 positivity was observed in 39% of 704 GCs and was negatively correlated with tumor differentiation, lymphovascular invasion, and tumor-node-metastasis stages. Notably, EPHB2 positivity was associated with better overall survival, and it was an independent prognostic marker in intestinal-type GCs. Overexpression of EPHB2 in GC cell lines, MKN-28 and MKN-74, reduced migration activity by suppressing phosphorylation of focal adhesion kinase, whereas no significant difference was observed in proliferation rates. Thus, we suggest that EPHB2 acts as a tumor suppressor in GCs and can be a prognostic marker in intestinal-type GCs.

Published
2022

24. Genetic Differentiation among Populations and Color Variants of Sea Cucumbers (Stichopus Japonicus) from Korea and China

Author

Jung-Ha Kang, Yi-Kyong Kim, Mi-Jung Kim, Jung-Yeon Park, Chul-Min An, Bong-Seok Kim, Je-Cheon Jun, Sang-Kyu Kim

Subjects
Biology (General), QH301-705.5
Abstract

The Far Eastern sea cucumber, Stichopus japonicus, is a favored food in Eastern Asia, including Korea, Japan, and China. Aquaculture production of this species has increased because of recent declines in natural stocks and government-operated stock release programs are ongoing. Therefore, the analyses of genetic structure in wild and hatchery populations are necessary to maintain the genetic diversity of this valuable marine resource. In addition, given that sea cucumber color affects market price, with the rare, possibly reproductively isolated, red type being the most valuable, an understanding of the genetic structure and diversity in color variation of green and red types is necessary. We analyzed the genetic structure of wild and hatchery-produced green type S. japonicus from Korea and China, and wild red type from Korea using 9 microsatellite makers. The number of alleles per locus ranged from 11 to 29 across all populations. The mean allele numbers of the green types from Korea (10.6) and China (10.1) were similar, but differed slightly from that of the red type (9.1). Pairwise multilocus FST and genetic distance estimations showed no significant differences between the green types from Korea and China, whereas the differences between the green and red types were significant. This was clearly illustrated by a UPGMA dendrogram, in which the two close subclusters of green types were completely separated from the red type. In addition, the allele frequencies of the green and red types were significantly different. Assignment tests correctly assigned 100% (quality index 99.97%) of individuals to their original color types and demonstrated the feasibility of microsatellite analysis for discrimination between color types.

Published
2011

29. Cancer Patients’ Willingness to Take COVID-19 Vaccination: A Nationwide Multicenter Survey in Korea

Author

Chun, June Young, primary, Kim, Se Ik, additional, Park, Eun Young, additional, Park, Sang-Yoon, additional, Koh, Su-Jin, additional, Cha, Yongjun, additional, Yoo, Heon Jong, additional, Joung, Jae Young, additional, Yoon, Hong Man, additional, Eom, Bang Wool, additional, Park, Chul Min, additional, Han, Ji-Youn, additional, Kim, Miso, additional, Lee, Dae-Won, additional, Kim, Jae-Weon, additional, Keam, Bhumsuk, additional, Lee, Maria, additional, Kim, Tae Min, additional, Choi, Young Ju, additional, Chang, Yoon Jung, additional, and Lim, Myong Cheol, additional

Published
2021
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30. Optimization of 2-Aminoquinazolin-4-(3 H)-one Derivatives as Potent Inhibitors of SARS-CoV-2: Improved Synthesis and Pharmacokinetic Properties.

Author

Shin, Young Sup, Lee, Jun Young, Jeon, Sangeun, Cho, Jung-Eun, Myung, Subeen, Jang, Min Seong, Kim, Seungtaek, Song, Jong Hwan, Kim, Hyoung Rae, Park, Hyeung-geun, Jeong, Lak Shin, and Park, Chul Min

Subjects
SARS-CoV-2, PHARMACOKINETICS
Abstract

We previously reported the potent antiviral effect of the 2-aminoquinazolin-4-(3H)-one 1, which shows significant activity (IC50 = 0.23 μM) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with no cytotoxicity. However, it is necessary to improve the in vivo pharmacokinetics of compound 1 because its area under the curve (AUC) and maximum plasma concentration are low. Here, we designed and synthesized N-substituted quinazolinone derivatives that had good pharmacokinetics and that retained their inhibitory activity against SARS-CoV-2. These compounds were conveniently prepared on a large scale through a one-pot reaction using Dimroth rearrangement as a key step. The synthesized compounds showed potent inhibitory activity, low binding to hERG channels, and good microsomal stability. In vivo pharmacokinetic studies showed that compound 2b had the highest exposure (AUC24h = 41.57 μg∙h/mL) of the synthesized compounds. An in vivo single-dose toxicity evaluation of compound 2b at 250 and 500 mg/kg in rats resulted in no deaths and an approximate lethal dose greater than 500 mg/kg. This study shows that N-acetyl 2-aminoquinazolin-4-(3H)-one 2b is a promising lead compound for developing anti-SARS-CoV-2 agents. [ABSTRACT FROM AUTHOR]

Published
2022
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35. Serotype Distribution and Antimicrobial Resistance of Invasive and Noninvasive Streptococcus pneumoniae Isolates in Korea between 2014 and 2016

Author

Park, Dong-Chul, primary, Kim, Si Hyun, additional, Yong, Dongeun, additional, Suh, In Bum, additional, Kim, Young Ree, additional, Yi, Jongyoun, additional, Song, Wonkeun, additional, Song, Sae Am, additional, Moon, Hee-Won, additional, Lee, Hae Kyung, additional, Park, Kyoung Un, additional, Kim, Sunjoo, additional, Jeong, Seok Hoon, additional, Lee, Jaehyeon, additional, Jeong, Joseph, additional, Kim, Yu Kyung, additional, Lee, Miae, additional, Cho, Jihyun, additional, Kim, Jong-Wan, additional, Shin, Kyeong Seob, additional, Hwang, Sang-Hyun, additional, Chung, Jae-Woo, additional, Woo, Hye In, additional, Lee, Chae Hoon, additional, Ryoo, Namhee, additional, Chang, Chulhun L., additional, Kim, Hyun Soo, additional, Kim, Jayoung, additional, Shin, Jong Hee, additional, Kim, Soo Hyun, additional, Lee, Mi-Kyung, additional, Lee, Seong Gyu, additional, Jang, Sook Jin, additional, Lee, Kyutaeg, additional, Suh, HunSuk, additional, Sohn, Yong-Hak, additional, Kwon, Min-Jung, additional, Lee, Hee Joo, additional, Hong, Ki Ho, additional, Woo, Kwang-Sook, additional, Park, Chul Min, additional, and Shin, Jeong Hwan, additional

Published
2019
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36. A Study on the Characteristics of Plan Composition shown in the Public Space of the Luxury Tourist Hotels on Seogwipo-si

Author

Park， Chul-Min

Subjects
Hotel design, Service (business), Engineering, business.industry, Advertising, Plan (drawing), Space (commercial competition), Unit (housing), Public space, Architectural plan, Marketing, business, ComputingMilieux_MISCELLANEOUS, Tourism
Abstract

Because hotels contain the cultural and artistic information of an era and plays a role as an iconic building to experience the unique regional culture, they are more than just a building. In recent years, as Jeju is emerging as a popular tourist city, a multi-functional and systematic plan for hotels is needed. Therefore, this study provides basic design data for hotel construction in the future by analyzing the public space of the luxury tourist hotels on Seogwipo-si. The public space of hotels, divided into service, food and beverage, banquet, leisure and convenience space, are categorized in terms of the cross combination type, entrance space form, plan type, unit space form to understand their relativity in the public space of hotels. This study reviewed the hotel construction based on the reference and literature, and, visited the sites to determine the current general status of hotels and then analyzed the architectural planning factors and spatial composition types.

Published
2016
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41. Discovery of Novel Small-Molecule Inhibitors of LIM Domain Kinase for Inhibiting HIV-1

Author

Yi, Fei, primary, Guo, Jia, additional, Dabbagh, Deemah, additional, Spear, Mark, additional, He, Sijia, additional, Kehn-Hall, Kylene, additional, Fontenot, Jacque, additional, Yin, Yan, additional, Bibian, Mathieu, additional, Park, Chul Min, additional, Zheng, Ke, additional, Park, Ha Jeung, additional, Soloveva, Veronica, additional, Gharaibeh, Dima, additional, Retterer, Cary, additional, Zamani, Rouzbeh, additional, Pitt, Margaret L., additional, Naughton, John, additional, Jiang, Yongjun, additional, Shang, Hong, additional, Hakami, Ramin M., additional, Ling, Binhua, additional, Young, John A. T., additional, Bavari, Sina, additional, Xu, Xuehua, additional, Feng, Yangbo, additional, and Wu, Yuntao, additional

Published
2017
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42. Study on Noise Reduction of DLP Front Home Theater Projector

Author

Park Chul Min, Park Dae Kyong, and Jang Dong Seob

Subjects
Engineering, business.industry, Noise reduction, Process (computing), Rotation, law.invention, Vibration, Noise, Optics, Projector, law, Color gel, Digital Light Processing, business, Computer Science::Cryptography and Security
Abstract

For the evaluation of acoustic noise of a DLP projector, vibration and sound characteristics of a DLP projector were studied. The acoustic noise of DLP projector could be classified into three categories, that is, the direct noise from a body of rotation, the air-bone noise generated from turbulence or vortex occurred during cooling process and the structural born noise produced by vibrating elements. Cooling fans and color filter wheel which rotates at 9000 rpm are main causes of acoustic noise induced in DLP projector. Since the structure of an optical module in a DLP projector can be excited by the excessive vibration of a color filter wheel, the structural design for anti-vibration should be considered. To make a reduction of overall acoustic noise, the anti-vibration design and the enclosing structure have been studied and applied to a color filter wheel.

Published
2004
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47. Mechanisms for DNA-damaging agent-induced inactivation of ErbB2 and ErbB3 via the ERK and p38 signaling pathways.

Author

Park, Chul Min, Kawasaki, Yuki, Refaat, Alaa, and Sakurai, Hiroaki

Subjects
*DNA damage, *EPIDERMAL growth factor receptors, *LUNG cancer, *CISPLATIN, *DOXORUBICIN
Abstract

Cisplatin (CDDP) and doxorubicin (DOX) are chemotherapeutic drugs that trigger apoptosis by inducing DNA-damage. A previous study using breast cancer cells demonstrated the negative feedback modulation of the epidermal growth factor receptor (EGFR) and receptor tyrosine-protein kinase erbB-2 (ErbB2) via extracellular signal-regulated kinase (ERK)-mediated phosphorylation of conserved Thr-669 and Thr-677 residues, respectively, in the juxtamembrane domain. In addition, CDDP has been identified to cause negative feedback inhibition of activated EGFR in lung cancer cells. In the present study, the role of phosphorylation in the feedback control of the ErbB2/ErbB3 heterodimer in human breast and gastric cancer cells was investigated. Phosphorylation of ErbB2 at Thr-677 was induced by CDDP and DOX, which in turn reduced tyrosine autophosphorylation of ErbB2 and ErbB3. Treatment with trametinib, a mitogen-activated protein kinase inhibitor that blocks ERK-mediated Thr-677 phosphorylation, and substitution of Thr-677 to alanine, blocked the feedback inhibition of ErbB2 and ErbB3. In addition, these agents caused the degradation of ErbB proteins through the activation of p38 mitogen-activated protein kinase (p38) and ERK. These results demonstrate that chemotherapeutic agents trigger ERK- and p38-mediated post-translational downregulation of ErbB receptors. [ABSTRACT FROM AUTHOR]

Published
2018
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48. Factors associated with antenatal depression in pregnant Korean females: the effect of bipolarity on depressive symptoms

Author

Park,Chul Min, Seo,Hye-Jin, Jung,Young-Eun, Kim,Moon-Doo, Hong,Seong-Chul, Bahk,Won-Myong, Yoon,Bo-Hyun, Hur,Min Hee, Song,Jae Min, Park,Chul Min, Seo,Hye-Jin, Jung,Young-Eun, Kim,Moon-Doo, Hong,Seong-Chul, Bahk,Won-Myong, Yoon,Bo-Hyun, Hur,Min Hee, and Song,Jae Min

Abstract

Chul Min Park,1 Hye-Jin Seo,2 Young-Eun Jung,3 Moon-Doo Kim,3 Seong-Chul Hong,4 Won-Myong Bahk,5 Bo-Hyun Yoon,6 Min Hee Hur,7 Jae Min Song31Department of Obstetrics and Gynecology, School of Medicine, Jeju National University, Jeju, 2Department of Psychiatry, Yeonkang Hospital, Jeju, 3Department of Psychiatry, 4Department of Preventive Medicine, School of Medicine, Jeju National University, Jeju, 5Department of Psychiatry, Yeouido St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, 6Department of Psychiatry, Naju National Hospital, Naju, 7School of Medicine, Jeju National University, Jeju, KoreaBackground: This cross-sectional study sought to identify factors associated with antenatal depression in pregnant Korean females, including sociodemographic parameters, social support, social conflict, and bipolarity.Methods: Eighty-four pregnant women were recruited to complete questionnaires on sociodemographic factors, obstetric history, depressive symptoms, and bipolarity. Depressive symptoms were assessed using the Korean version of the Edinburgh Postnatal Depression Scale. Bipolarity was assessed using the Korean version of the Mood Disorder Questionnaire.Results: Nineteen participants (22.6%) had positive Mood Disorder Questionnaire scores, suggesting the presence of bipolarity, and were significantly more likely to score high on the Edinburgh Postnatal Depression Scale. Antenatal depression was associated with bad marital communication and marital dissatisfaction.Conclusion: These results suggest that spousal interactions play a significant role in antenatal depression, and pregnant women with bipolarity may be more depressed than those without bipolarity.Keywords: antenatal depression, bipolarity, pregnancy, Korea

Published
2014

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