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( Keunwook Lee ),( Hyekyung Hwang ),( Ki Taek Nam ) The Editorial Office of Gut and Liver 2014 Gut and Liver Vol.8 No.2
Gastric cancer is the second most common cause of cancer-related death in the world. A growing body of evidence indi-cates that inflammation is closely associated with the initia-tion, progression, and metastasis of many tumors, including those of gastric cancer. In addition, approximately 60% of the world`s population is colonized by Helicobacter pylori, which accounts for more than 50% of gastric cancers. While the role of inflammation in intestinal and colonic cancers is relatively well defined, its role in stomach neoplasia is still unclear because of the limited access of pathogens to the acidic environment and the technical difficulties isolating and characterizing immune cells in the stomach, especially in animal models. In this review, we will provide recent updates addressing how inflammation is involved in gastric malignan-cies, and what immune characteristics regulate the patho-genesis of stomach cancer. Also, we will discuss potential therapeutics that target the immune system for the efficient treatment of gastric cancer. (Gut Liver 2014;8:131-139)
Control of macrophage responses on hydrophobic and hydrophilic carbon nanostructures
Chun, Young Wook,Wang, Wenping,Choi, Jungil,Nam, Tae-Hyun,Lee, Yong-Hee,Cho, Kwon-Koo,Im, Yeon-Min,Kim, Minsoo,Gwon, Yong-Hwan,Kang, Sang Soo,Lee, Jong Duk,Lee, Keunwook,Khang, Dongwoo,Webster, Thomas Elsevier 2011 Carbon Vol.49 No.6
<P><B>Abstract</B></P><P>This study monitored the expression of cytokines by macrophages and synaptic antigens on macrophages in contact with hydrophobic (water contact angle was 140°) and hydrophilic (water completely adsorbed within 5s) carbon nanostructures. Results indicated that hydrophilic carbon nanofibers (CNFs) generated the smallest inflammatory response from macrophages compared to hydrophobic CNFs and titanium (which is a conventional prosthetic implant material). Specifically, hydrophilic CNFs triggered less pro-inflammatory cytokine (e.g., tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)) secretion from macrophages than hydrophobic CNFs. Results further revealed that hydrophobic CNFs activated macrophage cytoskeleton changes in a time dependent manner, whereas hydrophilic CNFs did not. Lastly, although additional tests are needed, the net analysis of macrophage expression of co-stimulatory molecules (e.g., CD80 and CD86) demonstrated that hydrophobic CNFs may ultimately lead to increased T-cell activation than hydrophilic CNFs. In summary, this study suggests that the wettability of carbon nanostructured materials may be potentially linked to macrophage behavior to induce or minimize inflammation.</P>
mTOR directly phosphorylates p53 in PTEN-loss-induced cellular senescence
( Hyun Jung Hwang ),( Seung Hee Jung ),( Donghee Kang ),( Hyun A Park ),( Hyung Chul Lee ),( Daecheol Jeong ),( Keunwook Lee ),( Heon Joo Park ),( Young-gyu Ko ),( Jae-seon Lee ) 한국장기요양학회 2018 한국장기요양학회 추계학술대회자료집 Vol.2018 No.-
Loss of phosphatase and tensin homologue (PTEN), the major negative regulator of the PI3K/AKT pathway, triggers cellular senescence through a p53-dependent pathway called PTEN-loss-induced cellular senescence (PICS). Although the mTOR pathway has been consistently shown to have a critical function in cellular Senescence, the exact roles of mTORC1 and mTORC2 in PICS are not well known. In this study, we show that mTOR is a critical relay molecule downstream of PI3K/AKT and upstream of p53 in PICS. mTOR kinase, a major component of mTORC1 and mTORC2, directly binds p53 and phosphorylates it at serine 15. We found that mTORC1 and mTORC2 compete with MDM2 and increase the stability of p53, finally induces cellular senescence via accumulation of the cell cycle inhibitor, p21. In embryonic fibroblasts of PTEN-knockout mice, PTEN deficiency also induces mTORC1 and mTORC2 to bind to p53 instead of MDM2, leading to cellular senescence. These results collectively demonstrate that p53 phosphorylation at S15 by mTOR kinase activity is indispensable for PICS and active AKT-induced cellular senescence.
Metabolic influence on macrophage polarization and pathogenesis
( Bikash Thapa ),( Keunwook Lee ) 생화학분자생물학회(구 한국생화학분자생물학회) 2019 BMB Reports Vol.52 No.6
Macrophages play an essential role not only in mediating the first line of defense but also in maintaining tissue homeostasis. In response to extrinsic factors derived from a given tissue, macrophages activate different functional programs to produce polarized macrophage populations responsible for inducing inflammation against microbes, removing cellular debris, and tissue repair. However, accumulating evidence has revealed that macrophage polarization is pivotal in the pathophysiology of metabolic syndromes and cancer, as well as in infectious and autoimmune diseases. Recent advances in transcriptomic and metabolomic studies have highlighted the link between metabolic rewiring of macrophages and their functional plasticity. These findings imply that metabolic adaption to their surrounding microenvironment instructs activation of macrophages with functionally distinct phenotypes, which in turn probably leads to the pathogenesis of a wide spectrum of diseases. In this review, we have introduced emerging concepts in immunometabolism with focus on the impact on functional activation of macrophages. Furthermore, we have discussed the implication of macrophage plasticity on the pathogenesis of metabolic syndromes and cancer, and how the disease microenvironment manipulates macrophage metabolism with regard to the pathophysiology. [BMB Reports 2019; 52(6): 360-372]
공유형 자율차의 이동 경로 예측에 관한 기초연구: AI 분석 기반의 택시 경로와 도시 빅데이터를 이용하여
김건욱(KIM, Keunwook),김정화(KIM, Junghwa),김우진(KIM, Woojin),이승현(LEE, Seunghyeon) 대한교통학회 2021 대한교통학회지 Vol.39 No.6
본 연구에서는 대구광역시를 대상으로 택시 DTG(Digital Tachograph) 데이터를 활용하여 공유형 자율주행차의 주행 형태가 택시와 유사하다는 대전제를 두고 공유형 자율주행차의 주요 이동 경로를 예측하기 위한 기초연구를 수행하였다. 택시 이용자의 승차지점부터 하차지점까지의 주행 경로가 기록된 DTG 데이터를 바탕으로 승차율 분석결과를 히트맵으로 시각화하였으며, 주행 경로를 통해 택시의 주요 이동 경로를 확인하였다. 승차율 분석결과 대구광역시 도심인 동성로, 부도심인 동대구역의 승차율이 높게 나타났으며 그다음으로 승차율이 높은 지역은 상업시설의 비중이 높은 지역으로 확인되었다. 분석결과 지하철 노선과 도시 내 주간선도로와 유사한 축으로 나타나는 경향을 확인하였으며 이를 통해 향후 간선도로와 보조 간선도로, 지하철 노선을 따라 공유형 자율주행차를 위한 인프라가 구축 될 수 있다는 시사점을 얻을 수 있었다. 또한 머신러닝 기법인 랜덤포레스트와 LightGBM를 활용한 회귀모형을 구축하여 택시 이동 경로 결정에 영향을 주는 인자를 분석하였다. 모형 추정결과 2개의 회귀모형 모두 적합성을 확보한 것으로 나타났으며, 지하철역까지의 거리, 간선도로, 유동인구 수, 카드매출 실적, 버스정류장까지의 거리가 주요 변수로 도출되었다. 장래 이와 같은 영향변수들의 변화를 고려하여 공유형 자율주행차의 주행과 관련된 필수 인프라를 전략적으로 배치하는 데 에 본 연구의 결과가 활용 될 수 있을 것으로 기대한다. This study analyzed the main travel routes of shared autonomous vehicles by using DTG(Digital Tachograph) data of Daegu Metropolitan City under the premise that the driving mode of the shared autonomous vehicle is similar to that of a taxi. Based on the taxi DTG data that recorded the driving route from the taxi user’s entry point to the exit point, the ride rate analysis result was visualized as a heat map. The main travel routes of taxi users were found through the driving route. As a result of the loading rate analysis, it was confirmed that the loading rate was high in Dongseong-ro, the downtown area of Daegu Metropolitan City, and the nearby area of Dongdaegu Station. The following high passenger rate region was analyzed as the region with a high proportion of commercial facilities. In the case of movement routes, it was confirmed that they appear mainly along the same axis as subway lines and major arterial roads in the city. And through this, it was possible to obtain the implication that the infrastructure for shared autonomous vehicles could be built along arterial roads, auxiliary arterial roads, and subway lines in the future. In addition, this study established a regression model using machine learning techniques such as Random forest and LightGBM to confirm the variables that affect the user’s choice to use a taxi. The distance to the subway station, the arterial road, the number of floating population, the card sales performance, and the distance to the bus stop were derived as the primary variables that affect the decision of the taxi route. As a result of model estimation, it was found that both regression models secured the fit. It is expected that the results of this study can be utilized to strategically arrange essential infrastructure related to the driving of shared autonomous vehicles in consideration of changes in these influencing variables.
Maharjan, Sony,Park, Byoung Kwon,Lee, Su In,Lim, Yoonho,Lee, Keunwook,Kwon, Hyung-Joo The Korean Society of Applied Pharmacology 2018 Biomolecules & Therapeutics(구 응용약물학회지) Vol.26 No.3
A type of breast cancer with a defect in three molecular markers such as the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor is called triple-negative breast cancer (TNBC). Many patients with TNBC have a lower survival rate than patients with other types due to a poor prognosis. In this study, we confirmed the anti-cancer effect of a natural compound, Gomisin G, in TNBC cancer cells. Treatment with Gomisin G suppressed the viability of two TNBC cell lines, MDA-MB-231 and MDA-MB-468 but not non-TNBC cell lines such as MCF-7, T47D, and ZR75-1. To investigate the molecular mechanism of this activity, we examined the signal transduction pathways after treatment with Gomisin G in MDA-MB-231 cells. Gomisin G did not induce apoptosis but drastically inhibited AKT phosphorylation and reduced the amount of retinoblastoma tumor suppressor protein (Rb) and phosphorylated Rb. Gomisin G induced in a proteasome-dependent manner a decrease in Cyclin D1. Consequently, Gomisin G causes cell cycle arrest in the G1 phase. In contrast, there was no significant change in T47D cells except for a mild decrease in AKT phosphorylation. These results show that Gomisin G has an anti-cancer activity by suppressing proliferation rather than inducing apoptosis in TNBC cells. Our study suggests that Gomisin G could be used as a therapeutic agent in the treatment of TNBC patients.
( Sony Maharjan ),( Byoung Kwon Park ),( Su In Lee ),( Yoonho Lim ),( Keunwook Lee ),( Hyung-joo Kwon ) 한국응용약물학회 2018 Biomolecules & Therapeutics(구 응용약물학회지) Vol.26 No.3
A type of breast cancer with a defect in three molecular markers such as the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor is called triple-negative breast cancer (TNBC). Many patients with TNBC have a lower survival rate than patients with other types due to a poor prognosis. In this study, we confirmed the anti-cancer effect of a natural compound, Gomisin G, in TNBC cancer cells. Treatment with Gomisin G suppressed the viability of two TNBC cell lines, MDA-MB-231 and MDA-MB-468 but not non-TNBC cell lines such as MCF-7, T47D, and ZR75-1. To investigate the molecular mechanism of this activity, we examined the signal transduction pathways after treatment with Gomisin G in MDA-MB-231 cells. Gomisin G did not induce apoptosis but drastically inhibited AKT phosphorylation and reduced the amount of retinoblastoma tumor suppressor protein (Rb) and phosphorylated Rb. Gomisin G induced in a proteasome-dependent manner a decrease in Cyclin D1. Consequently, Gomisin G causes cell cycle arrest in the G1 phase. In contrast, there was no significant change in T47D cells except for a mild decrease in AKT phosphorylation. These results show that Gomisin G has an anti-cancer activity by suppressing proliferation rather than inducing apoptosis in TNBC cells. Our study suggests that Gomisin G could be used as a therapeutic agent in the treatment of TNBC patients.