• Title, Summary, Keyword: TRAIL

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Effects of Sodium Butyrate, a Histone Deacetylase Inhibitor, on TRAIL-mediated Apoptosis in Human Bladder Cancer Cells (인체 방광암세포에서 histone deacetylase 억제제인 sodium butyrate이 TRAIL에 의한 apoptosis 유도에 미치는 영향)

  • Han, Min-Ho;Choi, Yung Hyun
    • Journal of Life Science
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    • v.26 no.4
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    • pp.431-438
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    • 2016
  • The tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is considered a promising anticancer agent due to its unique ability to induce cancer cell death having only negligible effects on normal cells. However, many cancer cells tend to be resistant to TRAIL. In this study, we investigated the effects and molecular mechanisms of sodium butyrate (SB), a histone deacetylase inhibitor, in sensitizing TRAIL-induced apoptosis in 5637 human bladder cancer cells. Our results indicated that co-treatment with SB and TRAIL significantly increased the apoptosis induction, compared with treatment with either agent alone. Co-treatment with SB and TRAIL effectively increased the cell-surface expression of death receptor (DR) 5, but not DR4, which was associated with the inhibition of cellular Fas-associated death domain (FADD)-like interleukin-1β-converting enzyme (FLICE) inhibitory protein (c-FLIP). Furthermore, the activation of caspases (caspase-3, -8 and -9) and degradation of poly(ADP-ribose) were markedly increased in 5637 cells co-treated with SB and TRAIL; however, the synergistic effect was perfectly attenuated by caspase inhibitors. We also found that combined treatment with SB and TRAIL effectively induced the expression of pro-apoptotic Bax, cytosolic cytochrome c and cleave Bid to truncated Bid (tBid), along with down-regulation of anti-apoptotic Bcl-xL expression. These results collectively suggest that a combined regimen of SB plus TRAIL may offer an effective therapeutic strategy for safely and selectively treating TRAIL-resistant bladder cancer cells.

The Methods and Its Application of Long Distance Trail Planning in a Mountainous Region (산악지역에서의 장거리 트레일 조성 계획방법 및 적용)

  • Hwang, Guk-Woong;Jang, Byoung-Kwan
    • Journal of Korean Society of Rural Planning
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    • v.17 no.3
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    • pp.55-65
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    • 2011
  • Long distance trail or trail system planning is the first important step in transforming your vision into reality. Planning presents a vision for a trail or trail system and brings a comprehensive, long-range perspective. The master plan provides solid, credible recommendations for developing a trail or trail system that is safe, convenient, well used, supported by local residents, practicality to implement, and customized to meet the needs of the community, you will need to follow a logical planning. The key elements of master planning includes site assessment, vision, goals and objectives, routing and design, implementation strategies. Trails or trail systems should provide linkages to popular destinations, safely accommodate a variety of users, and be sensitive to any negative impacts on the natural environment and wildlife. Trails planners also need to think about how the trail, or trail system will function in the future as areas are developed or trail population increases. All of these factors during the planning process will ensure the existence of high-quality facilities for years to come. Project for Nakdong-jungmaek trail planning combine long distance trail with circuit way. That project is a planning brought out the best in each of Tokai natural way and Cotswold way. That is planning which is combined a wooded trail in Tokai natural way with access and facilities improving economy in Cotswold way. Also That planning embraces a core cultural center which is concerned forest or wood to come more people.

IRF-1-mediated IFN-γ enhancement of TRAIL-induced apoptosis (TRAIL 유도 세포사멸에 있어서 IFN-γ의한 증가 기전 연구: IRF-1과의 관련성)

  • Park, Sang-Youel;Seol, Jae-Won;Lee, You-Jin;Kang, Seog-Jin;Kim, In-shik;Kang, Hyung-sub;Chae, Joon-seok;Cho, Jong-Hoo
    • Korean Journal of Veterinary Research
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    • v.44 no.2
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    • pp.195-200
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    • 2004
  • Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF family and potent inducer of apoptosis. TRAIL has been shown to effectively limit tumor growth in vivo without detectable cytotoxic side effects. Interferon (IFN)-${\gamma}$ often modulates the anti-cancer activities of TNF family members including TRAIL. We previously reported that IFN-${\gamma}$ enhanced TRAIL-induced Apoptosis in HeLa cells without the unknown mechanism. In this study, we investigated whether IRF-1 involves in IFN-${\gamma}$-enhanced TRAIL-induced apoptosis. We exposed HeLa cells to IFN-${\gamma}$ for 12 hours and then treated with recombinant TRAIL protein. No apoptosis was induced in cells pretreated with IFN-${\gamma}$, and TRAIL only induced 30% apoptosis after 3 hours treatment. In HeLa cells pretreated with IFN-${\gamma}$, TRAIL induced cell death to more than 75% at 3 hours, showed that IFN-${\gamma}$-pretreatment enhanced HeLa cell death to TRAIL-induced apoptosis. To investigate the functional role of IRF-1 in IFN-${\gamma}$-enhanced TRAIL-induced apoptosis, IRF-1 was overexpressed by using an adenoviral vector AdIRF-1. IRF-1 overexpression increased apoptotic cell death and significantly enhanced apoptotic cell death induced by TRAIL when infected cells were treated with TRAIL. Our findings show that IFN-${\gamma}$ enhances TRAIL-induced apoptosis by IRF-1 in HeLa cells.

Induction of Apoptosis by Combination Treatment with Luteolin and TRAIL in T24 Human Bladder Cancer Cells (T24 방광암세포에서 Luteolin과 TRAIL의 복합 처리에 따른 Apoptosis 유도)

  • Park, Hyun Soo;Choi, Yung Hyun
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.42 no.9
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    • pp.1363-1369
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    • 2013
  • Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can selectively induce apoptosis by targeting cancer cells. However, some cancer cells are resistant to TRAIL-induced cytotoxicity. One method of overcoming TRAIL resistance is combination treatment with reagents to sensitize cells to TRAIL. Luteolin, a flavonoid, has been shown to have anti-cancer effects by inducing apoptosis and cell cycle arrest in various cancer cell lines in vitro. In this study, we investigated the effects of combination treatment with non-toxic concentration of TRAIL and luteolin in T24 human bladder cancer cells. Combined treatment with luteolin and TRAIL significantly inhibits cell proliferation via activation of caspases by inducing Bid truncation, up-regulation of Bax and down-regulation of X-linked inhibitor of apoptosis protein (XIAP). However, the apoptotic effects of combination treatment with luteolin and TRAIL were significantly inhibited by specific caspases inhibitors. Taken together, these results indicate that combination treatment with TRAIL and luteolin can induce apoptosis in TRAIL-resistant cancer cells through down-regulation of XIAP and modulation of tBid and Bax expression.

Enhancement of TRAIL-Mediated Apoptosis by Genistein in Human Hepatocellular Carcinoma Hep3B Cells: Roles of p38 MAPK Signaling Pathway (인체간암세포에서 genistein의 TRAIL에 의한 apoptosis 유도 상승효과에서 미치는 p38 MAPK signaling pathway의 영향)

  • Jin, Cheng-Yun;Park, Cheol;Park, Sang-Eun;Hong, Sang-Hoon;Choi, Yung-Hyun
    • Journal of Life Science
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    • v.21 no.11
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    • pp.1549-1557
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    • 2011
  • Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can selectively induce apoptosis in many types of transformed cells; however, some human hepatocellular carcinoma cells are particularly resistant to the effects of TRAIL. Although genistein, a natural isoflavonoid phytoestrogen, has been shown to have pro-apoptotic activity against human cancer cell lines, little is known about the mechanism of genistein in terms of TRAIL-induced apoptosis. In the present study, it was investigated whether or not combined treatment with genistein and TRAIL synergistically induced apoptosis in Hep3B hepatocarcinoma cells. Results indicate that treatment with TRAIL in combination with nontoxic concentrations of genistein sensitized TRAIL-resistant Hep3B cells to TRAIL-induced apoptosis, which was associated with mitochondrial dysfunction. Further, the inhibition of p38 mitogen-activated protein kinase (MAPK) activation markedly decreased genistein and TRAIL-induced cell viability and apoptosis by enhanced truncation of Bid, increase of pro-apoptotic Bax, decrease of anti-apoptotic Bcl-2, and release of cytochrome c from mitochondria to cytoplasm. Activation of caspases and degradation of poly (ADP-ribose) polymerase induced by the combined treatment was also markedly increased by the inhibition of p38 MAPK, through the mitochondrial amplification step. In conclusion, our data suggest that genistein sensitizes TRAIL-induced-apoptosis via p38 MAPK-dependent pathway.

A Study on Didactic Transposition Method and Students' Understanding for Graph's Trail (그래프의 경로에 대한 교수학적 변환 방식과 학생들의 이해 분석)

  • Shin, Bo-Mi
    • Journal of the Korean School Mathematics Society
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    • v.13 no.2
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    • pp.289-301
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    • 2010
  • This study discovered that instructional objectives of graphs which are dealt with in Math I of the revised curriculum are not matched with those of Discrete Mathematics in the 7th Curriculum. Based on the findings, this study analysed didactic transposition method of trail in graph and matrix of Math I and students' understanding about trail. Then this study discovered that though the concept definition of trail in Math I of the revised curriculum, some textbooks and students tend to consider it as the path. The concept definition of trail is significant in systems that deal with Euler Circuits(Euler Closed trail) and Hamilton Cycle. Then it is not easy to find the value of trail in Math I of the revised curriculum.

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Use Impacts on Environmental Deteriorations on and around Trails in Naesorak District of Soraksan National Park (설악산국립공원 내설악지구 등산로의 훼손 및 주연부식생)

  • 권태호;오구균;김보현
    • Korean Journal of Environment and Ecology
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    • v.11 no.4
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    • pp.523-534
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    • 1998
  • Six trails of Naesorak(west Sorak) district of Soraksan National Park were selected to investigate the use impacts on environmental edterioration of trail according to the different amount of use. The entire width, and slope of trail as the trail condition surveyed at the total of 132 points were significantly varied with the amount of use. Major deterioration types of trail were rock-exposure, root-exposure, deepening and divergence in order of frequency. Deteriorated points were significantly different in trail conditions from non-deteriorated points, and these latter generally appeared at the lowed altituede than the former on each trail. Naesorak district still seemed to have poorer use-impacts than Oesarak(east sorak) district. The dominant species in upper layer of trail edge vegetation differed from trail to trail, but in shrub layer Lespedeza maximowiczii, lindera obutsiloba for valley trail and Rhododendron schlipenbavhii for slope trail. The species diversity and coverage of shrub layer in trail edge were the highest on the Ose'am trail and each trail was dissimilar in species composition of shrub layer of edge vegetation.

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The Proteasome Inhibitor MG132 Sensitizes Lung Cancer Cells to TRAIL-induced Apoptosis by Inhibiting NF-κ Activation (폐암세포주에서 NFκ 활성 억제를 통한 Proteasome 억제제 MG132의 TRAIL-유도성 Apoptosis 감작 효과)

  • Seo, Pil Won;Lee, Kye Young
    • Tuberculosis and Respiratory Diseases
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    • v.65 no.6
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    • pp.476-486
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    • 2008
  • Background: TRAIL (TNF-related apoptosis inducing ligand) is a newly identified member of the TNF gene family which appears to have tumor-selective cytotoxicity due to the distinct decoy receptor system. TRAIL has direct access to caspase machinery and induces apoptosis regardless of p53 phenotype. Therefore, TRAIL has a therapeutic potential in lung cancer which frequently harbors p53 mutation in more than 50% of cases. However, it was shown that TRAIL also could activates $NF-{\kappa}B$ in some cell lines which might inhibit TRAIL-induced apoptosis. This study was designed to investigate whether TRAIL can activate $NF-{\kappa}B$ in lung cancer cell lines relatively resistant to TRAIL-induced apoptosis and inhibition of $NF-{\kappa}B$ activation using proteasome inhibitor MG132 which blocks $I{\kappa}B{\alpha}$ degradation can sensitize lung cancer cells to TRAIL-induced apoptosis. Methods: A549 (wt p53) and NCI-H1299 (null p53) lung cancer cells were used and cell viability test was done by MTT assay. Apoptosis was confirmed with Annexin V assay followed by FACS analysis. To study $NF-{\kappa}B$-dependent transcriptional activation, a luciferase reporter gene assay was used after making A549 and NCI-H1299 cells stably transfected with IgG ${\kappa}-NF-{\kappa}B$ luciferase construct. To investigate DNA binding of $NF-{\kappa}B$ activated by TRAIL, electromobility shift assay was used and supershift assay was done using anti-p65 antibody. Western blot was done for the study of $I{\kappa}B{\alpha}$ degradation. Results: A549 and NCI-H1299 cells were relatively resistant to TRAIL-induced apoptosis showing only 20~30% cell death even at the concentration 100 ng/ml, but MG132 ($3{\mu}M$) pre-treatment 1 hour prior to TRAIL addition greatly increased cell death more than 80%. Luciferase assay showed TRAIL-induced $NF-{\kappa}B$ transcriptional activity in both cell lines. Electromobility shift assay demonstrated DNA binding complex of $NF-{\kappa}B$ activated by TRAIL and supershift with p65 antibody. $I{\kappa}B{\alpha}$ degradation was proven by western blot. MG132 completely blocked both TRAIL-induced $NF-{\kappa}B$ dependent luciferase activity and DNA binding of $NF-{\kappa}B$. Conclusion: This results suggest that inhibition of $NF-{\kappa}B$ can be a potentially useful strategy to enhance TRAIL-induced tumor cell killing in lung cancer.

A Study on the Critical Factors of Determining Regional Trail Routes (광역 탐방로 노선설정을 위한 계획요소 연구)

  • Jung, Hui;Yang, Byoung-E.
    • Journal of the Korean Institute of Landscape Architecture
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    • v.36 no.5
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    • pp.35-41
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    • 2008
  • The purpose of this study is to determine those factors critical in the determining of regional trail routes. Initially, a consideration of the concept of the regional trail was conducted through literature reviews and 13 planning elements were determined from previous studies related to trail planning and trail construction studies. An additional 13 items were taken from literature research related to nature experiences or were sourced by interviewing experts. To verify these planning elements, a survey of experts was conducted. Individual elements were assessed concerning their degree of importance. As a result of this survey, it was found that the protection of ecologically sensitive areas and the use of existing trail routes are important route planning factors. These planning factors can be used for making decisions regarding regional trail route directions and situations.

Potentiation of TRAIL killing activity by multimerization through isoleucine zipper hexamerization motif

  • Han, Ji Hye;Moon, Ae Ran;Chang, Jeong Hwan;Bae, Jeehyeon;Choi, Jin Myung;Lee, Sung Haeng;Kim, Tae-Hyoung
    • BMB Reports
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    • v.49 no.5
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    • pp.282-287
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    • 2016
  • Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a homo-trimeric cytotoxic ligand. Several studies have demonstrated that incorporation of artificial trimerization motifs into the TRAIL protein leads to the enhancement of biological activity. Here, we show that linkage of the isoleucine zipper hexamerization motif to the N-terminus of TRAIL, referred as ILz(6):TRAIL, leads to multimerization of its trimeric form, which has higher cytotoxic activity compared to its native state. Size exclusion chromatography of ILz(6):TRAIL revealed possible existence of various forms such as trimeric, hexameric, and multimeric (possibly containing one-, two-, and multi-units of trimeric TRAIL, respectively). Increased number of multimerized ILz(6):TRAIL units corresponded with enhanced cytotoxic activity. Further, a high degree of ILz(6):TRAIL multimerization triggered rapid signaling events such as activation of caspases, tBid generation, and chromatin condensation. Taken together, these results indicate that multimerization of TRAIL significantly enhances its cytotoxic activity.