• Asian Pacific Journal of Cancer Prevention
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• 제14권9호
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• pp.5199-5205
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• 2013

Background/Aim: The Hippo signaling pathway is a newly discovered and conserved signaling cascade, which regulates organ size control by governing cell proliferation and apoptosis. This study aimed to investigate its effects in human gastric cancer. Methods: Tumor tissues (n=60), adjacent non-tumor tissues (n=60) and normal tissues (n=60) were obtained from the same patients with primary gastric cancer (GC). In addition, 70 samples of chronic atrophic gastritis (CAG) tissues were obtained from patients with intestinal metaplasia (IM) by endoscopic biopsy. Hippo signaling molecules, including Mst1, Lats1, YAP1, TAZ, TEAD1, Oct4 and CDX2, were determined by quantitative polymerase chain reaction (qPCR). Protein expression of Mst1, Lats1, YAP1, TEAD1 and CDX2 was assessed by immunohistochemistry and Western blotting. Results: Mst1, Lats1 and Oct4 mRNA expression showed an increasing tendency from GC tissues to normal gastric tissues, while the mRNA expression of YAP1, TAZ and TEAD1 was up-regulated (all P<0.01). Mst1 and Lats1 protein expression presented a similar trend with their mRNA expression. In addition, YAP1 and TEAD1 protein expression in GC was significantly higher than in the other groups (all P<0.01). CDX2 mRNA and protein expression in the CAG group were higher than in the other groups (all P<0.01). In GC, mRNA expression of Mst1, Lats1, Oct4, YAP1, TAZ, TEAD1 and CDX2 had a close correlation with lymphatic metastasis and tumor TNM stage (all P<0.01). Furthermore, protein expression of Mst1, Lats1, YAP1, TAZ, TEAD1 and CDX2 had a close correlation between each other (P<0.05). Conclusion: The Hippo signaling pathway is involved in the development, progression and metastasis of human gastric cancer. Therefore, manipulation of Hippo signaling molecules may be a potential therapeutic strategy for gastric cancer.

• Transactions on Electrical and Electronic Materials
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• 제12권2호
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• pp.80-83
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• 2011

We have fabricated phosphorescent white organic light-emitting devices (WOLEDs) with a spin-coated poly(Nvinylcarbazole) [PVK] host layer. Iridium(III) bis[(4,6-difluorophenyl)-pyridinato-N,$C^{2'}$]picolinate (FIrpic), tris(2-phenylpyridine)iridium(III) [$Ir(ppy)_3$], and tris(2-phenyl-1-quinoline)iridium(III) [$Ir(phq)_3$], were used as the blue, green, and red guest materials, respectively. The PVK was mixed with FIrpic, $Ir(ppy)_3$, and $Ir(phq)_3$ molecules in a chlorobenzene solution and spin-coated in order to prepare the emission layer; 3-(4-biphenylyl)-4-phenyl-5-(4-tertbutylphenyl)-1,2,4-triazole (TAZ) was used as an electron transport material. The resultant device structure was ITO/PVK:FIrpic:$Ir(ppy)_3:Ir(phq)_3$/TAZ/LiF/Al. The electroluminescence, efficiency, and electrical conduction characteristics of the WOLEDs based on the doped PVK host layer were investigated. The maximum current efficiency of the three wavelength WOLED with the doped PVK host was 19.2 cd/A.

• BMB Reports
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• 제51권3호
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• pp.143-150
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• 2018

The Hippo signaling pathway plays an essential role in adult tissue homeostasis and organ size control. Abnormal regulation of Hippo signaling can be a cause for multiple types of human cancers. Since the awareness of the importance of the Hippo signaling in a wide range of biological fields has been continually grown, it is also understood that a thorough and well-rounded comprehension of the precise dynamics could provide fundamental insights for therapeutic applications. Several components in the Hippo signaling pathway are known to be targeted for proteasomal degradation via ubiquitination by E3 ligases. ${\beta}-TrCP$ is a well-known E3 ligase of YAP/TAZ, which leads to the reduction of YAP/TAZ levels. The Hippo signaling pathway can also be inhibited by the E3 ligases (such as ITCH) which target LATS1/2 for degradation. Regulation via ubiquitination involves not only complex network of E3 ligases but also deubiquitinating enzymes (DUBs), which remove ubiquitin from its targets. Interestingly, non-degradative ubiquitin modifications are also known to play important roles in the regulation of Hippo signaling. Although there has been much advanced progress in the investigation of ubiquitin modifications acting as regulators of the Hippo signaling pathway, research done to date still remains inadequate due to the sheer complexity and diversity of the subject. Herein, we review and discuss recent developments that implicate ubiquitin-mediated regulatory mechanisms at multiple steps of the Hippo signaling pathway.

• 한국동물학회:학술대회논문집
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• 한국동물학회 2001년도 한국생물과학협회 학술발표대회
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• pp.239.1-239
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• 2001

No Abstract, See Full Text

• 동의생리병리학회지
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• 제33권4호
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• pp.191-197
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• 2019

This study aims to evaluate the effects of the root bark of Morus alba (RMA) on the regulation of the Hippo-YAP pathway. Hippo-YAP signaling is a critical regulator in controlling organ size and tissue homeostasis. Hippo, the serine/threonine kinase phosphorylate the LATS. Phosphorylated LATS then phosphorylates and inactivates the YAP and TAZ, which are two closely related transcriptional co-activator. Here we report RMA activates the Hippo signaling, thereby inhibits the YAP/TAZ activity. First, we examine the cytotoxic effects of RMA by MTT assay. RMA was cytotoxic at concentrations higher than $50{\mu}g/ml$ in HEK293A cells. The reporter gene assay was performed to measure the activity of TEAD, a key transcription factor that controls cell growth and proliferation. RMA significantly suppressed the luciferase activity. By phos-taq gel shift assay, and western blotting, we showed that RMA enhanced the phosphorylation of YAP in wild type cells, but not in LATS1/2 knock out cells, which means RMA activates classical Hippo pathway. RMA induced the cytoplasmic sequestration of YAP. RMA also suppressed the mRNA expression of CTGF and CYR61; the two major YAP dependent genes. Taken together, RMA is considered to be a good candidate for proliferative disease such as cancer, by facilitating cell death through activating the Hippo signaling pathway.

• IMMUNE NETWORK
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• 제20권5호
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• pp.36.1-36.13
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• 2020

Hippo signaling pathways are evolutionarily conserved signal transduction mechanisms mainly involved in organ size control, tissue regeneration, and tumor suppression. However, in mammals, the primary role of Hippo signaling seems to be regulation of immunity. As such, humans with null mutations in STK4 (mammalian homologue of Drosophila Hippo; also known as MST1) suffer from recurrent infections and autoimmune symptoms. Although dysregulated T cell homeostasis and functions have been identified in MST1-deficient human patients and mouse models, detailed cellular and molecular bases of the immune dysfunction remain to be elucidated. Although the canonical Hippo signaling pathway involves transcriptional co-activator Yes-associated protein (YAP) or transcriptional coactivator with PDZ motif (TAZ), the major Hippo downstream signaling pathways in T cells are YAP/TAZ-independent and they widely differ between T cell subsets. Here we will review Hippo signaling mechanisms in T cell immunity and describe their implications for immune defects found in MST1-deficient patients and animals. Further, we propose that mutual inhibition of Mst and Akt kinases and their opposing roles on the stability and function of forkhead box O and β-catenin may explain various immune defects discovered in mutant mice lacking Hippo signaling components. Understanding these diverse Hippo signaling pathways and their interplay with other evolutionarily-conserved signaling components in T cells may uncover molecular targets relevant to vaccination, autoimmune diseases, and cancer immunotherapies.

• 한국정보디스플레이학회:학술대회논문집
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• 한국정보디스플레이학회 2003년도 International Meeting on Information Display
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• pp.903-906
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• 2003

Doping a small amount of a phosphorescent dye into an organic light-emitting diodes(OLED) can lead to a significant improvement in the device properties. The fluorescent host materials like TAZ, CBP have been used, but have a problem of rapid decay of efficiency at high current densities. To alleviate this problem, phosphorescent host was introduced. The whole configuration of OELD fabricated was ITO/a-NPD(50nm)/Zn $cluster:Ir(ppy)_{3}(30nm)/BCP{(10nm)/Alq_{3}(20nm)$ /Al:Li. The OLED showed high luminance (> 50,000 $cd/m^{2}$ ) and external efficiency(5.7%). At higher current densities, rapid decay of external quantum efficiency or host emission, which was frequently observed in the fluorescent host system, were not observed.

• 한국전기전자재료학회논문지
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• 제26권9호
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• pp.682-685
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• 2013

We have fabricated blue phosphorescent organic light-emitting devices (OLEDs) on a plastic substrate. The solution coated poly (9-vinylcarbazole) (PVK) host doped with Bis (3,5-difluoro-2-(2-pyridyl)phenyl_(2-carboxypyridyl)irdium(III) (FIrPic) guest molecules was used as an hole transporting emission layer. The device structure was ITO/PVK:FIrpic (50 nm, xwt%)/TAZ 50 nm)/LiF (0.5 nm)/Al (100 nm). The concentration of FIrpic molecule was varied from 1 wt% to 10 wt%. The OLED on plastic substrate exhibited maximum current efficiency of 18 cd/A with 5 wt% FIrpic molecules were doped into the PVK layer.

• 대한교통학회지
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• 제29권1호
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• pp.17-27
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• 2011

본 연구에서는 교통수요분석의 중요한 오차요인 가운데 하나인 존 체계 구축에 따른 교통수요 추정 결과의 영향을 국가교통DB 전국 지역 간 자료를 이용하여 실증적으로 살펴보고 이를 통하여 현재 배포되는 Network 수준 및 해당사업(고속도로, 국도, 국지도 및 지방도 / 차로수)에 따른 적정 존 체계 수준, 내부 통행비율 수준 등에 대한 결과를 비교분석하였다. 더불어, 존 체계 수준에 따라 교통수요 추정 결과의 정확도가 도로위계, 도로용량별로 어떻게 달라지는지를 검토하였다. 마지막으로, 국가교통DB의 전국 지역 간 자료의 적정한 존 체계 수준을 제시해 보았다. 본 연구에서는 사회경제변수를 고려한 적정 Centroid의 위치와 Connector 연결지점 및 개수 등 존 체계를 구축하였으며, 존 체계 구축이 교통수요 추정에 어떤 영향을 미치는지를 살펴보기 위해 F-test와 상관계수 분석, 평균통행거리 및 통행시간분석, 오차율 분석, 총 주행거리 분석 등을 수행하였다. 분석 결과, 도로위계, 도로용량에 따라 적정 존체계 수준이 다양하게 나타났다. 즉, 현재의 시군구 단위 존 수준에서 추가적인 존 세분화를 수행할수록 국도, 국지도 및 지방도 / 편도 1차로 도로의 교통수요 추정 결과 신뢰성이 전반적으로 개선됨을 확인할 수 있었다. 특히, 신뢰성 높은 교통수요 추정 결과를 확보하기 위해서는 되도록 읍면동 단위의 존 수준까지 존 세분화를 수행할 필요가 있음을 확인할 수 있었다.

• BMB Reports
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• 제50권12호
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• pp.599-600
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• 2017

Many studies have focused on the tumor suppressive role of $TGF-{\beta}$ signaling during the early stages of tumorigenesis by activating the target genes involved in cytostasis and apoptosis. We investigated the effects of $TGF-{\beta}$ inhibition on early tumorigenesis in the liver, by employing diverse inhibitory methods. Strikingly, $TGF-{\beta}$ inhibition consistently suppressed hepatic tumorigenesis that was induced either by activated RAS plus p53 downregulation or by the co-activation of RAS and TAZ signaling; this demonstrates the requirements for canonical $TGF-{\beta}$ signaling in tumorigenesis. Moreover, we found that Snail is the target gene of the $TGF-{\beta}$ signaling pathway that promotes hepatic carcinogenesis. The knockdown of Snail suppressed the early tumorigenesis in the liver, as did the $TGF-{\beta}$ inhibition, while the ectopic expression of Snail restored tumorigenesis that was suppressed by the $TGF-{\beta}$ inhibition. Our findings establish the oncogenic $TGF-{\beta}$-Smad-Snail signaling axis during the early tumorigenesis in the liver.