• Title/Summary/Keyword: Promising target

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MST1R as a potential new target antigen of chimeric antigen receptor T cells to treat solid tumors

  • Wen An;Ju-Seop Kang;Sukjoong Oh;Ang Tu
    • The Korean Journal of Physiology and Pharmacology
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    • v.27 no.3
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    • pp.241-256
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    • 2023
  • Although chimeric antigen receptor T cell (CAR-T) is a promising immunotherapy in hematological malignancies, there remain many obstacles to CART cell therapy for solid tumors. Identifying appropriate tumor-associated antigens (TAAs) is especially critical for success. Using a bioinformatics approach, we identified common potential TAAs for CAR-T cell immunotherapy in solid tumors. We used the GEO database as a training dataset to find differentially expressed genes (DEGs) and verified candidates using the TCGA database, obtaining seven common DEGs (HM13, SDC1, MST1R, HMMR, MIF, CD24, and PDIA4). Then, we used MERAV to analyze the expression of six genes in normal tissues to determine the ideal target genes. Finally, we analyzed tumor microenvironment factors. The results of major microenvironment factor analyses showed that MDSCs, CXCL1, CXCL12, CXCL5, CCL2, CCL5, TGF- β, CTLA-4, and IFN-γ were significantly overexpressed in breast cancer. The expression of MST1R was positively correlated with TGF- β, CTLA-4, and IFN-γ. In lung adenocarcinoma, MDSCs, Tregs, CXCL12, CXCL5, CCL2, PD-L1, CTLA-4, and IFN-γ were significantly overexpressed in tumor tissues. The expression of MST1R was positively correlated with TGF- β, CTLA-4, and IFN-γ. In bladder cancer, CXCL12, CCL2, and CXCL5 were significantly overexpressed in tumor tissues. MST1R expression was positively correlated with TGF- β. Our results demonstrate that MST1R has the potential as a new target antigen for treating breast cancer, lung adenocarcinoma, and bladder cancer and may be used as a progression indicator for bladder cancer.

Targeting cell surface glucose-regulated protein 94 in gastric cancer with an anti-GRP94 human monoclonal antibody

  • Hyun Jung Kim;Yea Bin Cho;Kyun Heo;Ji Woong Kim;Ha Gyeong Shin;Eun-bi Lee;Seong-Min Park;Jong Bae Park;Sukmook Lee
    • BMB Reports
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    • v.57 no.4
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    • pp.188-193
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    • 2024
  • Gastric cancer (GC), a leading cause of cancer-related mortality, remains a significant challenge despite recent therapeutic advancements. In this study, we explore the potential of targeting cell surface glucose-regulated protein 94 (GRP94) with antibodies as a novel therapeutic approach for GC. Our comprehensive analysis of GRP94 expression across various cancer types, with a specific focus on GC, revealed a substantial overexpression of GRP94, highlighting its potential as a promising target. Through in vitro and in vivo efficacy assessments, as well as toxicological analyses, we found that K101.1, a fully human monoclonal antibody designed to specifically target cell surface GRP94, effectively inhibits GC growth and angiogenesis without causing in vivo toxicity. Furthermore, our findings indicate that K101.1 promotes the internalization and concurrent downregulation of cell surface GRP94 on GC cells. In conclusion, our study suggests that cell surface GRP94 may be a potential therapeutic target in GC, and that antibody-based targeting of cell surface GRP94 may be an effective strategy for inhibiting GRP94-mediated GC growth and angiogenesis.

The Influence of Unattended Distractors on the Identification of Targets (주의하지 않은 방해자극이 표적의 식별에 미치는 영향)

  • Park, ChangHo
    • Korean Journal of Cognitive Science
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    • v.24 no.4
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    • pp.365-391
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    • 2013
  • Negative repetition effect (NRE) refers to the phenomenon that the accuracy of report is impaired when a target was flanked by the same distractor than when by alternative distractor. To probe the nature of NRE, this study introduced attention window(s) indicating the positions where a target might be presented, and non-attention window(s) where a target could not be presented. Attention windows are supposed to help participants detect targets readily. Two among three positions are indicated by attention windows in Exp. 1, and a single large attention window encompassing central two positions among four positions was used in Exp. 2, and either large or small attention window was used depending on the number of target candidates in Exp. 3. In the result of three experiments, NREs were consistently observed when both positions of a target and a distractor were indicated by previous attention windows. However, NREs (including its tendency) and its opposite, PREs were observed when a distractor was presented in the non-attention position, depending on its distance from the target and the size of attention window. It seems that this pattern of repetition effects is hard to be explained by repetition blindness hypothesis (Kanwisher, 1991), positional uncertainty hypothesis (Keren & Boer, 1985), and inhibitory attention capture hypothesis (Kwak et al., 1993). Instead it was proposed that shifting of spatial attention should be considered accordingly with the structure of stimulus display. The promising role of this task was discussed in studying the relation of attention and perception.

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An Approach to the Market Analysis of KoreaSat Services

  • Park, Myeong-Cheol;Choi, Hyuk-Jun
    • ETRI Journal
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    • v.15 no.2
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    • pp.53-68
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    • 1993
  • The field of marketing research in the satellite communication services is still in the early stage of its development. Particularly, in Korean domestic satellite service market, many theoretical and methodological opportunities now exist. In this paper we develop a model, which identifies target markets and promising application services in Korean satellite communication service Market. One key contribution of this paper is a modeling approach to the assessment of market potential and priorities of the application services in each Korean industry. We define and estimate the degree of attractiveness for each segmented market which represents the market potential estimated by current usage of terrestrial services and each market segment's willingness to adopt satellite technology. Since all possible satellite application services are not equally important in the market, they should be differentiated in terms of the likelihood of success. We introduce another index prioritizing application services by tying together three important factors affecting Korean satellite service demand. Some marketing implications of model results are also discussed. Finally the findings of our model are compared with those of other similar studies.

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Identification of Potent Leukocyte Common Antigen-Related Phosphatase Inhibitors via Structure-Based Virtual Screening

  • Park, Hwangseo;Pham, Ngoc Chien;Chun, Ha-Jung;Ryu, Seong Eon
    • Bulletin of the Korean Chemical Society
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    • v.34 no.7
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    • pp.2006-2010
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    • 2013
  • Leukocyte common antigen-related phosphatase (LAR) has been considered a promising target for the development of therapeutics for neurological diseases. Here, we report the first example for a successful application of the structure-based virtual screening to identify the novel small-molecule LAR inhibitors. Five of these inhibitors revealed micromolar inhibitory activities with the associated $IC_{50}$ values ranging from 2 to 6 ${\mu}M$. Because the newly identified inhibitors were also screened for having desirable physicochemical properties as a drug candidate, they may serve as a starting point of the structure-activity relationship study to optimize the medical efficacy. Structural features relevant to the stabilization of the new inhibitors in the active site of LAR are discussed in detail.

SDRE controller considering Multi Observer applied to nonlinear IPMC model

  • Bernat, Jakub;Kolota, Jakub;Stepien, Slawomir
    • Smart Structures and Systems
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    • v.20 no.1
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    • pp.1-10
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    • 2017
  • Ionic Polymer Metal Composite (IPMC) is an electroactive polymer (EAP) and a promising candidate actuator for various potential applications mainly due to its flexible, low voltage/power requirements, small and compact design, and lack of moving parts. Although widely used in industry, this material requires accurate numerical models and knowledge of optimal control methods. This paper presents State-Dependent Riccati Equation (SDRE) approach as one of rapidly emerging methodologies for designing nonlinear controllers. Additionally, the present paper describes a novel method of Multi HGO Observer design. In the proposed design, the calculated position of the IPMC strip accurately tracks the target position, which is illustrated by the experiments. Numerical results and comparison with experimental data are presented and the effectiveness of the proposed control strategy is verified in experiments.

A Proposal of Hybrid Cooling System Coupled with Radiation Panel Cooling and Natural Ventilation (자연환기와 복사냉방을 병용한 하이브리드 시스템의 제안)

  • 송두삼
    • Korean Journal of Air-Conditioning and Refrigeration Engineering
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    • v.15 no.6
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    • pp.543-550
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    • 2003
  • In order to saving the energy for HVAC system of buildings, utilization of wind-induced cross ventilation is thought to be promising. However, utilization of natural ventilation alone is not sufficient for maintaining the human thermal-comfort such as in hot and humid regions. A hybrid air conditioning system with a controlled natural ventilation system, or combination of natural ventilation with mechanical air conditioning is thought to overcome the deficiency of wind-driven cross ventilation and to have significant effects on energy reduction. This paper describes a concept of hybrid system and propose a new type of hybrid system using radiational cooling with wind-induced cross ventilation. Moreover, a radiational cooling system is compared with an all-air cooling system. The characteristics of the indoor environment will be examined through CFD (Computational Fluid Dynamics) simulation, which is coupled with a radiation heat transfer simulation and with HVAC control in which the PMV value for the human model in the center of the room is controlled to attain the target value.

The Hsp90 chaperone machinery: from structure to drug development

  • Hahn, Ji-Sook
    • BMB Reports
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    • v.42 no.10
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    • pp.623-630
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    • 2009
  • Hsp90, an evolutionarily conserved molecular chaperone, is involved in the folding, stabilization, activation, and assembly of a wide range of 'client' proteins, thus playing a central role in many biological processes. Especially, several oncoproteins act as Hsp90 client proteins and tumor cells require higher Hsp90 activity than normal cells to maintain their malignancy. For this reason, Hsp90 has emerged as a promising target for anti-cancer drug development. It is still largely unknown how Hsp90 can recognize structurally unrelated client proteins. However, recent progress in structural studies on Hsp90 and its interaction with various co-chaperones has broadened our knowledge of how the Hsp90 ATPase activity, which is essential for its chaperone function, is regulated and coupled with the conformational changes of Hsp90 dimer. This review focuses on the roles of various Hsp90 co-chaperones in the regulation of the Hsp90 ATPase cycle, as well as in the selection of client proteins. In addition, the current development of Hsp90 inhibitors based on the structural information will be discussed.

Synthesis and Biological Activities of (4-Arylpiperazinyl)piperidines as Nonpeptide BACE 1 Inhibitors

  • Boja, Poojary;Won, Sun-Woo;Suh, Dong-Hoon;Chu, Jeong-Hyun;Park, Woo-Kyu;Lim, Hee-Jong
    • Bulletin of the Korean Chemical Society
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    • v.32 no.4
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    • pp.1249-1252
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    • 2011
  • Inhibition of BACE 1 activity is considered as a promising therapeutic target for Alzheimer's Disease (AD). Synthesis and inhibitory activities of (4-arylpiperazinyl)piperidines by bioisosteric replacement of a biaryl group with an arylpiperazine as BACE 1 inhibitors are described. The resulting (4-arylpiperazinyl)piperidines represent novel nonpeptide BACE 1 inhibitors with improved in vitro potency.

Cyclooxygenase-2 as a Molecular Target for Cancer Chemopreventive Agents

  • Surh, Young-Joon
    • Toxicological Research
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    • v.17
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    • pp.89-96
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    • 2001
  • Recently, considerable attention has been focused on the role of cyclooxygenase-2 (COX-2) in the carcinogenesis as well as in inflammation. Improperly overexpressed COX-2 has been observed in many types of human cancers and transformed cells in culture. Thus, it is conceivable that targeted inhibition of abnormally or improperly up-regulated COX-2 provides one of the most effective and promising strategies for cancer prevention. A ubiquitous eukaryotic transcription factor, NF-kB is considered to be involved in regulation of COX-2 expression. Furthermore, extracellular-regulated protein kinase and p38 mitogen-activated protein (MAP) kinase appear to be key elements of the intracellular signaling cascades involved in NF-kB activation in response to a wide array of external stimuli. Certain chemopreventive phytochemicals suppress activation of NF-kB by blocking one or more of the MAP kinases, which may contribute to their inhibitory effects on COX-2 induction. One of the plausible mechanisms by which chemopreventive phytochemicals inhibit NF-kB activation involves suppression of degradation of the inhibitory unit I kB, which hampers subsequent translocation of p65, the functionally active subunit of NF-kB.

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