• Title/Summary/Keyword: Activation Strategy

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Simultaneous destabilization of β-catenin and Ras via targeting of the axin-RGS domain as a potential therapeutic strategy for colorectal cancer

  • Cha, Pu-Hyeon;Choi, Kang-Yell
    • BMB Reports
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    • v.49 no.9
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    • pp.455-456
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    • 2016
  • Mutations of APC and KRAS are frequently observed in human colorectal cancers (CRCs) and the Wnt/β-catenin and Ras pathways are consequently activated in a significant proportion of CRC patients. Mutations in these two genes are also known to synergistically induce progression of CRCs. Through a series of studies, we have demonstrated that inhibition of the Wnt/β-catenin signaling pathway negatively regulates Ras stability, therefore, Ras abundance is increased together with β-catenin in both mice and human CRCs harboring adenomatous polyposis coli (APC) mutations. In a recent study, we identified KY1220, a small molecule that simultaneously degrades β-catenin and Ras by inhibition of the Wnt/β-catenin pathway, and obtained its derivative KYA1797K, which has improved activity and solubility. We found that KYA1797K binds the RGS domain of axin and enhances the binding affinity of β-catenin or Ras with the β-catenin destruction complex components, leading to simultaneous destabilization of β-catenin and Ras via GSK3β activation. By using both in vitro and in vivo studies, we showed that KYA1797K suppressed the growth of CRCs harboring APC and KRAS mutations through destabilization of β-catenin and Ras. Therefore, our findings indicate that the simultaneous destabilization of β-catenin and Ras via targeting axin may serve as an effective strategy for inhibition of CRCs.

Resveratrol Suppresses CD4+ T Cell Activation and Differentiation in vitro (Resveratrol의 CD4+ T 세포 활성과 분화 억제 효과)

  • Seo, Dong-Won;Yi, Young-Joo;Lee, Sang-Myeong
    • Korean Journal of Plant Resources
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    • v.27 no.5
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    • pp.567-575
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    • 2014
  • Resveratrol is a naturally occurring stilbene which is safe and well-described compound with a potent anti-inflammatory activity. Recent studies suggested that resveratrol suppressed various inflammation mediated diseases such as asthma, chronic colitis, rheumatoid arthritis, and type 1 diabetes. These studies indicated that resveratrol might directly modulate $CD4^+$ helper T cells (Th cells)-mediated immune responses. However, it is not fully elucidated whether resveratrol directly regulates $CD4^+$ Th cell activation and differentiation. In the present study, $CD4^+$ Th cells were purified from C57BL/6 and treated with various concentrations of resveratrol. We found that resveratrol directly suppressed $CD4^+$ Th cells activation, leading to a defect in T cell proliferation. When $CD4^+$ Th cells were treated with resveratrol, cytokine production was also significantly reduced in a dose dependent manner. In accordance with these results, resveratrol even inhibited $CD4^+$ Th cells differentiation into Th1, Th2 or Th17, which produces IFN-${\gamma}$, IL-4 or IL-17 respectively. We also found that resveratrol could induce apoptosis of $CD4^+$ T cells at a high concentration. Our data demonstrated that resveratrol inhibited directly $CD4^+$ Th cells activation and differentiation. It suggests that resveratrol could be an efficient therapeutic strategy for autoimmune diseases in which $CD4^+$ Th cells play a critical role.

Phenotype Changes in Immune Cell Activation in Obesity (비만 환경 내 면역세포 활성화 표현형의 변화)

  • Ju-Hwi Park;Ju-Ock Nam
    • Journal of Life Science
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    • v.33 no.3
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    • pp.295-303
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    • 2023
  • Immune and metabolic systems are important factors in maintaining homeostasis. Immune response and metabolic regulation are highly associated, so, when the normal metabolism is disturbed, the immune response changed followed the metabolic diseases occur. Likewise, obesity is highly related to immune response. Obesity, which is caused by an imbalance in energy metabolism, is associated with metabolic diseases, such as insulin resistance, type 2 diabetes, fatty liver diseases, atherosclerosis and hypertension. As known, obesity is characterized in chronic low-grade inflammation. In obesity, the microenvironment of immune cells became inflammatory by the unique activation phenotypes of immune cells such as macrophage, natural killer cell, T cell. Also, the immune cells interact each other in cellular or cytokine mechanisms, which intensify the obesity-induced inflammatory response. This phenomenon suggests the possibility of regulating the activation of immune cells as a pharmacological therapeutic strategy for obesity in addition to the common pharmacological treatment of obesity which is aimed at inhibiting enzymes such as pancreatic lipase and α-amylase or inhibiting differentiation of preadipocytes. In this review, we summarize the activation phenotypes of macrophage, natural killer cell and T cell, and their aspects in obesity. We also summarize the pharmacological substances that alleviates obesity by regulating the activation of immune cells.

A Study on the Determinants of Purchasing Decision Making for Effective Branding Strategy: Focusing the Medicine Treatment in Infantile Obesity (효과적인 브랜딩 전략을 위한 소비자 구매의사 결정 요인 분석: 소아비만 치료제 유통시장을 중심으로)

  • Park, Mun-Seo;Kim, Hyung-Joon;Lee, Sang-Youn
    • Journal of Distribution Science
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    • v.9 no.3
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    • pp.55-64
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    • 2011
  • This study is important in its focus to find key clues in the marketing strategy, consumer behavior, and communication processes that define the infantile obesity market. The study, the first of its kind, surveyed a target audience, purchasing group, and housewives in their quest to determine purchasing decisions and effective branding strategy planning for the infantile obesity market. Another key component of the study was to focus on the key direct and/or indirect distribution channels for the subject market. Recently, obesity has emerged as a major social concern; some studies show that the onslaught of an adverse eating culture in Korea emanates from the prevalence of fast-food dining establishments. Obesity among children leads to adult obesity, especially if the young people's parents are overweight; notably, if either one or both of the parents are obese, the percentage of young people eventually being obese is approximately 80 to 85 percent. Because obesity is the cause of many major health concerns later in life, the struggle for a healthy life is considerably adversely affected by parents' consumer behavior. Infantile obesity, resulting in adult obesity, is also an important national economic and social issue. The sizable direct and indirect economic costs, as well as the tremendous social costs of obesity, cannot be overstated. Effective food branding and advertising centered on food preferences and dietary behaviors, especially to children, creates an effective marketing effort that, ultimately, leads to positive results. Thus, the purpose of this study is to demonstrate that the treatment of childhood obesity in Korea, through the activation of a brand and retail market, can effectively solve social and economic problems that result from infantile and childhood obesity. In this study, obesity markets and distribution channels in the purchase decision-making factors determining factor based on it effective inspection and branding strategies and brand marketing communications strategy proposed measures contribute to the obesity drug market and further enable the childhood obesity problem is intended to assist in solving.

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A Study on Design Medical Tourism Strategy and Business Service Model (의료관광 전략 수립 및 비즈니스 서비스 모델 설계에 관한 연구)

  • Chang, Sae Kyung;Baek, Jong Sun
    • The Journal of Society for e-Business Studies
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    • v.22 no.3
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    • pp.43-55
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    • 2017
  • The market for medical tourism services in the world is steadily increasing and the medical tourism market in the South Korea is also showing high growth. However, they have also problem such as informal various information and services, irregularity price competition etc. In order to solve this problem, We have designed a medical tourism service model based on ICT specific on domestic medical ecosystem. First, analysis trends of domestic and overseas medical ecosystem and identify current problem of medical tourism. In order to solve existed problem we also have designed a medical tourism strategy. Based on the strategy, we have designed business service model based on ICT platform for as fit as Korea medical tourism status. The proposed medical tourism business service model can provide usability to customer and also can solve current medical tourism problem. We expect industrial effect and contribution to the activation.

A Study on the Analysis and Application Strategy of the Characters Developed by the Local Governments - Focused on the Characters of 31 Cities and Goons of Gyeonggi Province - (지방자치단체 캐릭터 분석 및 활용전략에 관한 연구 - 경기도 31개 시ㆍ군의 캐릭터를 중심으로 -)

  • 정현원;한광식
    • Archives of design research
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    • v.16 no.4
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    • pp.129-140
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    • 2003
  • As the importance of Culture Technology (music, publication, mobile, film, video, cartoon, animation, character, game, broadcasting etc) is increased, the field of character industry recently has been recognized as an independent brand value beyond the existing view point of simple designing; it also has been given much attention as a main axis leading the cultural industry of the 21 st century. The character of a local government plays roles such as a symbolic part of a region, parts of tourism and public relations, and a profit-making function, which results into generation of regional image and activation of regional economy. However, the present application strategy of the character is only limited to an early stage of regional advertisements. In this context, this study is aimed to investigate and analyze the character development of local governments, especially 31 cities and goons of Gyeonggi Province, comparing with those of local governments of Japan. In the long run, this will provide some suggestions for strategy of character applications. Then, this research is expected to be used as basic reference materials for character development of other local governments and government agencies.

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City Marketing Strategy using City Identities -Focus on the Application of Modern Architectures- (도시 정체성을 통한 도시마케팅 전략 도출 -근대역사물의 활용 사례를 중심으로-)

  • Seo, Yong-Mo;Chun, Myung-Hwan;Kim, Hyung-Jun
    • The Journal of the Korea Contents Association
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    • v.10 no.6
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    • pp.297-306
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    • 2010
  • A city is the space which has a various historical experiment and memories. From these social and cultural environment, regional competitions through the introduction and settlement of a local self-government have been important in city marketing. For city development, a serial activation policies are come and in this process the native history and cultures have recognized as the core tool of cities. For possession of city competition, we have developed the cities' tangible and/or intangible cultural properties and make full use of a attractive asset. The city identity is established and the opportunity of a special space is made. This city identity has been dependent on spending time. We suggest the strategy for the historical and cultural city image through the historical element and the development of program for the promotion of publicity activities. The preservation and application of the modern architectures as the cultural and historical element promote the city image and build the position of city identity. We suggest the city marketing application strategy for the implication on the sustainable reproductive city.

On-the-fly Estimation Strategy for Uncertainty Propagation in Two-Step Monte Carlo Calculation for Residual Radiation Analysis

  • Han, Gi Young;Kim, Do Hyun;Shin, Chang Ho;Kim, Song Hyun;Seo, Bo Kyun;Sun, Gwang Min
    • Nuclear Engineering and Technology
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    • v.48 no.3
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    • pp.765-772
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    • 2016
  • In analyzing residual radiation, researchers generally use a two-step Monte Carlo (MC) simulation. The first step (MC1) simulates neutron transport, and the second step (MC2) transports the decay photons emitted from the activated materials. In this process, the stochastic uncertainty estimated by the MC2 appears only as a final result, but it is underestimated because the stochastic error generated in MC1 cannot be directly included in MC2. Hence, estimating the true stochastic uncertainty requires quantifying the propagation degree of the stochastic error in MC1. The brute force technique is a straightforward method to estimate the true uncertainty. However, it is a costly method to obtain reliable results. Another method, called the adjoint-based method, can reduce the computational time needed to evaluate the true uncertainty; however, there are limitations. To address those limitations, we propose a new strategy to estimate uncertainty propagation without any additional calculations in two-step MC simulations. To verify the proposed method, we applied it to activation benchmark problems and compared the results with those of previous methods. The results show that the proposed method increases the applicability and user-friendliness preserving accuracy in quantifying uncertainty propagation. We expect that the proposed strategy will contribute to efficient and accurate two-step MC calculations.

Government as a Platform Revitalization Strategy Derived from Webtoon Platform Success Factors (웹툰플랫폼 성공요인에서 도출한 플랫폼 정부 활성화 방안)

  • Seo, Hyungjun
    • Journal of Digital Convergence
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    • v.19 no.10
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    • pp.1-13
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    • 2021
  • This study postulates that Government as a Platform(GaaP) could be a next generation government model, drawing activation strategy from success factors of webtoon platform by NAVER. It suggests success factors of Naver webtoon case based on three main components of platform strategy. First, in the aspect of platform infrastructure, Naver webtoon was established based on powerful portal site by parent company Naver and improved platform accessibility through using webtoon without login. Second, in the aspect of stakeholder engagement, Naver webtoon has offed webtoon at no cost and it has taken an intermediary role for supporting the stakeholders with PPS. Third, in the aspect of outputs production, Naver webtoon offered real time feedback from webtoon users that could affect webtoon production and established incubating system that allow users to create their webtoon. And due to PPS, it makes possible to various create second outputs based on webtoon, which can contribute to activating webtoon ecosystem.

Modulation of Autophagy is a Potential Strategy for Enhancing the Anti-Tumor Effect of Mebendazole in Glioblastoma Cells

  • Jo, Seong Bin;Sung, So Jung;Choi, Hong Seok;Park, Jae-Sung;Hong, Yong-Kil;Joe, Young Ae
    • Biomolecules & Therapeutics
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    • v.30 no.6
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    • pp.616-624
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    • 2022
  • Mebendazole (MBZ), a microtubule depolymerizing drug commonly used for the treatment of helminthic infections, has been suggested as a repositioning candidate for the treatment of brain tumors. However, the efficacy of MBZ needs further study to improve the beneficial effect on the survival of those patients. In this study, we explored a novel strategy to improve MBZ efficacy using a drug combination. When glioblastoma cells were treated with MBZ, cell proliferation was dose-dependently inhibited with an IC50 of less than 1 µM. MBZ treatment also inhibited glioblastoma cell migration with an IC50 of less than 3 µM in the Boyden chamber migration assay. MBZ induced G2-M cell cycle arrest in U87 and U373 cells within 24 h. Then, at 72 h of treatment, it mainly caused cell death in U87 cells with an increased sub-G1 fraction, whereas polyploidy was seen in U373 cells. However, MBZ treatment did not affect ERK1/2 activation stimulated by growth factors. The marked induction of autophagy by MBZ was observed, without any increased expression of autophagy-related genes ATG5/7 and Beclin 1. Co-treatment with MBZ and the autophagy inhibitor chloroquine (CQ) markedly enhanced the anti-proliferative effects of MBZ in the cells. Triple combination treatment with temozolomide (TMZ) (another autophagy inducer) further enhanced the anti-proliferative effect of MBZ and CQ. The combination of MBZ and CQ also showed an enhanced effect in TMZ-resistant glioblastoma cells. Therefore, we suggest that the modulation of protective autophagy could be an efficient strategy for enhancing the anti-tumor efficacy of MBZ in glioblastoma cells.