• Title/Summary/Keyword: NOTCH1

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Propranolol Inhibits the Proliferation of Human Glioblastoma Cell Lines through Notch1 and Hes1 Signaling System

  • Kim, Hyun Sik;Park, Young Han;Lee, Heui Seung;Kwon, Mi Jung;Song, Joon Ho;Chang, In Bok
    • Journal of Korean Neurosurgical Society
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    • v.64 no.5
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    • pp.716-725
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    • 2021
  • Objective : The anti-tumor effect of the beta-adrenergic receptor antagonist propranolol in breast cancer is well known; however, its activity in glioblastoma is not well-evaluated. The Notch-Hes pathway is known to regulate cell differentiation, proliferation, and apoptosis. We investigated the effect of propranolol to human glioblastoma cell lines, and the role of Notch and Hes signaling in this process. Methods : We performed immunohistochemical staining on 31 surgically resected primary human glioblastoma tissues. We also used glioblastoma cell lines of U87-MG, LN229, and neuroblastoma cell line of SH-SY5Y in this study. The effect of propranolol and isoproterenol on cell proliferation was evaluated using the MTT assay (absorbance 570 nm). The impact of propranolol on gene expression (Notch and Hes) was evaluated using real-time polymerase chain reaction (RT-PCR, whereas protein levels of Notch1 and Hes1 were measured using Western blotting (WB), simultaneously. Small interfering RNA (siRNA) was used to suppress the Notch gene to investigate its role in the proliferation of glioblastoma. Results : Propranolol and isoproterenol caused a dose-dependent decrease in cell proliferation (MTT assay). RT-PCR showed an increase in Notch1 and Hes1 expression by propranolol, whereas WB demonstrated increase in Notch1 protein, but a decrease in Hes1 by propranolol. The proliferation of U87-MG and LN229 was not significantly suppressed after transfection with Notch siRNA. Conclusion : These results demonstrated that propranolol suppressed the proliferation of glioblastoma cell lines and neuroblastoma cell line, and Hes1 was more closely involved than Notch1 was in glioblastoma proliferation.

Notch Signal Transduction Induces a Novel Profile of Kaposi's Sarcoma-Associated Herpesvirus Gene Expression

  • Chang Hee-Soon
    • Journal of Microbiology
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    • v.44 no.2
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    • pp.217-225
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    • 2006
  • Kaposi's sarcoma-associated herpesvirus (KSHV) RTA transcription factor is recruited to its responsive elements through interaction with RBP-Jk that is a downstream transcription factor of the Notch signaling pathway that is important in development and cell fate determination. This suggests that KSHV RTA mimics cellular Notch signal transduction to activate viral lytic gene expression. Here, I demonstrated that unlike other B lymphoma cells, KSHV -infected primary effusion lymphoma BCBL1 cells displayed the constitutive activation of ligand-mediated Notch signal transduction, evidenced by the Jagged ligand expression and the complete proteolytic process of Notch receptor I. In order to investigate the effect of Notch signal transduction on KSHV gene expression, human Notch intracellular (hNIC) domain that constitutively activates RBP-Jk transcription factor activity was expressed in BCBL1 cells, TRExBCBL1-hNIC, in a tetracycline inducible manner. Gene expression profiling showed that like RTA, hNIC robustly induced expression of a number of viral genes including KS immune modulatory gene resulting in downregulation of MHC I and CD54 surface expression. Finally, the genetic analysis of KSHV genome demonstrated that the hNIC-mediated expression of KS during viral latency consequently conferred the downregulation of MHC I and CD54 surface expression. These results indicate that cellular. Notch signal transduction provides a novel expression profiling of KSHV immune deregulatory gene that consequently confers the escape of host immune surveillance during viral latency.

Design of a 170 GHz Notch Filter for the KSTAR ECE Imaging Sensor Application

  • Mohyuddin, Wahab;Woo, Dong Sik;Kim, Sung Kyun;Kim, Kang Wook;Choi, Hyun-Chul
    • Journal of Sensor Science and Technology
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    • v.25 no.1
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    • pp.8-12
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    • 2016
  • A planar, light-weight, and low-cost notch filter structure is required for the KSTAR ECEI (Electron Cyclotron Emission Imaging) system to protect the mixer arrays from spurious plasma heating power. Without protection, this heating power can significantly degrade or damage the performance of the mixer array. To protect mixer arrays, a frequency selective surface (FSS) structure is the suitable choice as a notch filter to reject the spurious heating power. The FSS notch filter should be located between the lenses of the ECEI system. This paper presents a 170 GHz FSS notch filter for the KSTAR ECEI sensor application. The design of such an FSS notch filter is based on the single-sided square loop geometry, because that makes it relatively insensitive to the incident angle of incoming wave. The FSS notch filter exhibits high notch rejection with low pass-band insertion loss over a wide range of incident angles. This paper also reviews the simulated and measured results. The proposed FSS notch filter might be implemented in other millimeter-wave plasma devices.

siRNA-mediated Silencing of Notch-1 Enhances Docetaxel Induced Mitotic Arrest and Apoptosis in PCa Cells

  • Ye, Qi-Fa;Zhang, Yi-Chuan;Peng, Xiao-Qing;Long, Zhi;Ming, Ying-Zi;He, Le-Ye
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.6
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    • pp.2485-2489
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    • 2012
  • Purpose: Notch is an important signaling pathway that regulates cell fate, stem cell maintenance and the initiation of differentiation in many tissues. It has been reported that activation of Notch-1 contributes to tumorigenesis. However, whether Notch signaling might have a role in chemoresistance of prostate cancer is unclear. This study aimed to investigate the effects of Notch-1 silencing on the sensitivity of prostate cancer cells to docetaxel treatment. Methods: siRNA against Notch-1 was transfected into PC-3 prostate cancer cells. Proliferation, apoptosis and cell cycle distribution were examined in the presence or absence of docetaxel by MTT and flow cytometry. Expression of $p21^{waf1/cip1}$ and Akt as well as activation of Akt in PC-3 cells were detected by Western blot and Real-time PCR. Results: Silencing of Notch-1 promoted docetaxel induced cell growth inhibition, apoptosis and cell cycle arrest in PC-3 cells. In addition, these effects were associated with increased $p21^{waf1/cip1}$ expression and decreased Akt expression and activation in PC-3 cells. Conclusion: Notch-1 promotes chemoresistance of prostate cancer and could be a potential therapeutic target.

Dynamic Fracture Toughness of Chevron-notch Ceramic Specimens measured in Split Hopkinson Pressure Bar

  • Lee, Yeon-Soo;Yoon, Young-Ki;Yoon, Hi-Seak
    • International Journal of Precision Engineering and Manufacturing
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    • v.3 no.3
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    • pp.69-75
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    • 2002
  • Measuring dynamic fracture toughness of brittle and small ceramic specimen is very difficult in a SHPB (Split Hopkinson Pressure Bar). As a countermeasure to this difficulty, a dynamic fracture toughness measuring method by the Chevron-notch ceramic specimen was proposed. Tested chevron specimens were of Chevron notch angles of 90$^{\circ}$, 100$^{\circ}$ and 110$^{\circ}$. Through finite element analysis, shape parameters of the Chevron-notch specimens according to notch angles were calculated. And the static fracture tough1ess of the Chevron-notch alumina specimen was measured as 3.8MPa√m similar to that of CT specimen with a precrack. Dynamic fracture toughness was 4.5MPa√m slightly higher than the static one. It was shown in this study that the proposed Chevron-notch specimens are valid to measure dynamic fracture toughness of extremely brittle materials such as ceramic.

Failure Behaviors Depending on the Notch Location of the Impact Test Specimens on the HAZ (용접열영향부 충격시험편 노치 위치에 따른 파괴거동)

  • Jang, Yun-Chan;Hong, Jae-Keun;Park, Ji-Hong;Kim, Dong-Wook;Lee, Young-Seog
    • Proceedings of the KSME Conference
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    • 2007.05a
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    • pp.706-711
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    • 2007
  • Numerical studies were performed to examine the effects of notch location of impact specimens on the failure behavior of HAZ (heat affected zone) when Charpy V-notch impact test were made at a low temperature ($1^{\circ}C$). Carbon steel plate (SA-516 Gr. 70) with thickness of 25mm for pressure vessel was welded by SMAW (shielded metal-arc welding) and specimens were fabricated from the welded plate. Charpy tests were then performed with specimens having different notch positions of specimens varying from the fusion line through HAZ to base metal. A series of finite element analysis which simulates the Charpy test and crack propagation initiating at the tip of V-notch was carried out as well. The finite element analysis takes into account the irregular fusion line and non-homogenous material properties due to the notch location of the specimen in HAZ. Results reveals that the energies absorbed during impact test depend significantly on the notch location and direction of specimen. Finite element analysis also demonstrates that the notch location of specimens, to a great extent, influences the reliability and consistency of the test.

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Implementation of Power Line Communication System Appling High-Order Stable Notch filter Scheme (High-Order Stable Notch Filter 기법을 적용한 전력선 통신 시스템 구현)

  • Kim, Kyung-Seok;Nam, Yun-Ho;Kim, Joo-Seok
    • The Journal of Korean Institute of Communications and Information Sciences
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    • v.36 no.1C
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    • pp.28-36
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    • 2011
  • As Power Line has been already installed over 60% of a residential area all over the world, Broadband Service has been possible using high-speed PLC(Power Line Communication) without new access line installed for Internet access. Because of such reason, PLC is researched as the most suitable service for Last Mile Solution. But, Power Line is designed for transmitting electric power, so peripheral Wireless Communication System is affected by a leak of electric wave. In this paper, we propose a High Performance Notch Filter algorithm in comparison with a existing notch filter for reduction of interference between existing Wireless Communication Service and Power Line Service. In addition, we implement the Notch Filter emulator appling a High Performance Notch Filter and using a embedded board.

An Evaluation of Notch Shpae for Estimation of Available $K_{1d}$ by Instrumented Charpy Impact Test (유효 $K_{1d}$ 산정을 위한 샬피 충격시험편의 노치형상에 관한 연구)

  • 우창기;강동명;이하성
    • Transactions of the Korean Society of Automotive Engineers
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    • v.7 no.6
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    • pp.135-143
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    • 1999
  • This investigation evaluates effects of notch depth, fatigue precrack length and side groove in impact specimen for estimation of a valid K1d by instrumented Charpy impact test. Specimen material is 6005-T6. for notch depth 2.0mm and 2.5mm specimens or within about 2mm fatigue precrack length with notch depth 2.0mm and 2.5mm specimens or within about 2mm fatigue precrack length with notch depth 2.0mm , dynamic fracture toughness [$K_{1d,(1)}$] obtained by crack initiation load($P_m$) should be used. Dynamic fracture toughness of side grooved specimens are overestimated to that of standard impact specimen about 15 %-20%. It is confirmed that the formula of dynamic fracture toughness obtained by impact absorbed energy is inappropriate for ductile materials.

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Role of Sp in the Regulation of Notch1 Gene Expression by Curcumin (커큐민에 의한 노치발현 조절에서 Sp의 역할)

  • Park, Seon-Yeong;Kang, Yong-Gyu;Bae, Yun-Hee;Kim, Su-Ryun;Park, Hyun-Joo;Kang, Young-Soon;Kim, Mi-Kyoung;Wee, Hee-Jun;Jang, Hye-Ock;Bae, Moon-Kyoung;Woo, Jae Suk;Bae, Soo-Kyung
    • KSBB Journal
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    • v.28 no.1
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    • pp.1-6
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    • 2013
  • Curcumin has diverse anticancer activities that lead to tumor growth inhibition of cancer cells and induction of apoptosis. Curcumin is involved in the regulation of multiple genes via transcription factors including NF-${\kappa}B$, STATs, AP1, and SP. Notch signaling plays critical roles in maintaining the balance between cell proliferation, differentiation and apoptosis, and thereby may contribute to the development of various cancers involving breast cancer. This study was to investigate the effects of curcumin on Notch1 gene expression and to explore the underlying mechanism. Here, we found that curcumin decreased the levels of Notch1 mRNA and protein in MDA-MB-231 human breast cancer cells, along with the downregulation of Sp family genes (Sp1, Sp2, Sp3, and Sp4). The repressive effect of curcumin on Notch1 gene transcription was confirmed by performing Notch1 promoter-driven reporter assay and three Sp-binding sites were identified on Notch1 promoter that may act as curcumin-respose elements. Moreover, treatment with mitramycin A, a specific Sp inhibitor, decreased the levels of Notch1 mRNA and protein in human breast cancer cells. Taken together, our results indicate that Notch1 gene expression is downregulated by curcumin, at least in part, through the suppression of Sp family, which may lead to apoptosis in human breast cancer cells.

Study of tensile behavior of Y shape non-persistent joint using experimental test and numerical simulation

  • Sarfarazi, V.;Hajiloo, M.;Ghalam, E. Zarrin;Ebneabbasi, P.
    • Computers and Concrete
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    • v.26 no.6
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    • pp.565-576
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    • 2020
  • Experimental and discrete element methods were used to investigate the effects of angle of Y shape non-persistent joint on the tensile behaviour of joint's bridge area under brazilian test. concrete samples with diameter of 100 mm and thikness of 40 mm were prepared. Within the specimen, two Y shape non-persistent notches were provided. The large notch lengths were 6 cm, 4 cm and 2 cm. the small notch lengths were 3 cm, 2 cm and 1 cm. The angle of larger notch related to horizontal axis was 0°, 30°, 60°, 90°. Totally, 12 different configuration systems were prepared for Y shape non-persistent joints. Also, 18 models with different Y shape non-persistent notch angle and notch length were prepared in numerical model. The large notch lengths were 6 cm, 4 cm and 2 cm. the small notch lengths were 3 cm, 2 cm and 1 cm. The angle of larger notch related to horizontal axis was 0, 30, 60, 90, 120 and 150. Tensile strength of model materil was 1 MPa. The axial load was applied to the model by rate of 0.02 mm/sec. This testing showed that the failure process was mostly governed by the Y shape non-persistent joint angle and joint length. The tensile strengths of the specimens were related to the fracture pattern and failure mechanism of the discontinuities. It was shown that the tensile behaviour of discontinuities is related to the number of the induced tensile cracks which are increased by increasing the joint length and joint angle. The minimum tensile strength occurs when the angle of larger joint related to horizontal axis was 60°. Also, the maximum compressive strength occurs when the angle of larger joint related to horizontal axis was 90°. The tensile strength was decreased by increasing the notch length. The failure pattern and failure strength are similar in both methods i.e. the experimental testing and the numerical simulation methods.