• Title/Summary/Keyword: ERB

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Overexpression of EFGR as Prognostic Factor and Effect of EGF in the Progression of Hypopharyngeal Cancer (하인두암에서 예후인자로서의 표피성장인자수용체(EGFR) 과발현과 하인두암의 진행에 있어 표피성장인자(EGF)의 역할 분석)

  • Lim, Young Chang;Choi, Eun Chang;Kim, Yoon Tae;Kim, Jang Hee;Hwang, Hye Sook;Kang, Sung Un;Chang, Jae Won;Shin, Yoo Seob;Kim, Chul-Ho
    • Korean Journal of Head & Neck Oncology
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    • v.29 no.1
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    • pp.1-10
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    • 2013
  • 연구배경 및 목적 표피성장인자수용체(EGFR)는 HER2/neu(erbB2), HER3(erbB3), HER4(erbB4)를 포함하는 receptor tyrosine ki-nase의 erbB 그룹에 속하는 수용체이다. 표피성장인자수용체의 과발현은 다양한 종류의 암, 특히 두경부편평세포암에서 예후를 악화시킨다고 알려져 있다. 이에 저자들은 하인두편평세포암에서 표피성장인자수용체의 발현 및 분포를 확인하고, 하인두암에서 표피성장인자(EGF)가 암세포의 증식과 침습에 미치는 영향에 대해 알아보고자 하였다. 대상 및 방법 57명의 하인두편평세포암 환자의 조직에서 표피성장인자수용체의 발현을 면역화학적염색을 통해 확인하고, 이에 대해 임상병리학적 요인과 생존율에 대한 분석을 시행하고, 일부 환자의 정상 및 암조직에서 Western blot을 시행하였다. 하인두편평세포암 세포주인 FaDu에서 proliferative assay, colony dispersion, wound healing assay, invasion assay를 시행하여, 하인두암의 진행에서 표피성장인자의 역할에 대하여 분석하였다. 또한 RT-PCR과 Zymography를 통하여 Matrix metalloproteinase(MMP)-2, 9의 발현을 확인하였다. 결 과 63.2%의 하인두편평세포암 조직에서 표피성장인자수용체의 발현이 확인되었다. 표피성장인자수용체의 발현은 정상조직에서 비하여 하인두암 조직에서 유의하게 증가되어 있었으며, 병리학적 병기(p=0.022)가 올라갈수록 유의하게 증가하였으나, 증례수의 제한으로 생존율에서는 통계적 유의성을 얻지는 못했다(p=0.053). in vitro의 결과로 표피성장인자를 FaDu 세포주에 처리하였을 때, FaDu 세포주의 증식이 유의하게 증가되었으며(p<0.05), Transwell invasion chamber상 침습의 증가가 확인되었다(p<0.05). RT-PCR과 zymogram 실험상 표피성장인자처리시 FaDu 세포주의 MMP-2, 9이 발현이 증가되고 활성화되는 것이 확인하였다. 결 론 본 연구에서 표피성장인자수용체의 과발현이 하인두암의 예후 인자로서의 가능성을 확인하였고, 표피성장인자가 하인두편평세포암의 증식과 침습에 관여하는 것을 확인하였다.

The Assessment on the Sound Quality of Reduced Frequency Selectivity of Hearing Impaired People (난청인의 주파수 선택도 둔화현상이 음질에 미치는 영향 평가)

  • An, Hong-Sub;Park, Gyu-Seok;Jeon, Yu-Yong;Song, Young-Rok;Lee, Sang-Min
    • The Transactions of The Korean Institute of Electrical Engineers
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    • v.60 no.6
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    • pp.1196-1203
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    • 2011
  • The reduced frequency selectivity is a typical phenomenon of sensorineural hearing loss. In this paper, we compared two modeling methods for reduced frequency selectivity of hearing impaired people. The two models of reduced frequency selectivity were made using LPC(linear prediction coding) algorithm and bandwidth control algorithm based on ERB(equivalent rectangular bandwidth) of auditory filter, respectively. To compare the effectiveness of two models, we compared the result of PESQ (perceptual evaluation of speech quality) and LLR(log likelihood ratio) using 36 Korean words of two syllables. To verify the effect on noise condition, we mixed white and babble noise with 0dB and -3dB SNR to speech words. As the result, it is confirmed that the PESQ score of bandwidth control algorithm is higher than the score of LPC algorithm, on the other hands, and the LLR score of LPC algorithm is lower than the score of bandwidth control algorithm. It means that both non-linearity and widen auditory filter characteristics caused by reduced frequency selectivity could be more reflected in bandwidth control algorithm than in LPC algorithm.

Endocytic Regulation of EGFR Signaling

  • Chung, Byung-Min
    • Interdisciplinary Bio Central
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    • v.4 no.2
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    • pp.3.1-3.7
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    • 2012
  • Epidermal growth factor receptor (EGFR) is a member of the ErbB family (ErbB1-4) of receptor tyrosine kinases (RTKs). EGFR controls numerous physiological functions, including cell proliferation, migration, differentiation and survival. Importantly, aberrant signaling by EGFR has been linked to human cancers in which EGFR and its various ligands are frequently overexpressed or mutated. EGFR coordinates activation of multiple downstream factors and is subject of various regulatory processes as it mediates biology of the cell it resides in. Therefore, many studies have been devoted to understanding EGFR biology and targeting the protein for the goal of controlling tumor in clinical settings. Endocytic regulation of EGFR offers a promising area for targeting EGFR activity. Upon ligand binding, the activated receptor undergoes endocytosis and becomes degraded in lysosome, thereby terminating the signal. En route to lysosome, the receptor becomes engaged in activating various signaling pathways including PI-3K, MAPK and Src, and endocytosis may offer both spatial and temporal regulation of downstream target activation. Therefore, endocytosis is an important regulator of EGFR signaling, and increasing emphasis is being placed on endocytosis in terms of cancer treatment and understanding of the disease. In this review, EGFR signaling pathway and its intricate regulation by endocytosis will be discussed.

EBP1 regulates Suv39H1 stability via the ubiquitin-proteasome system in neural development

  • Kim, Byeong-Seong;Ko, Hyo Rim;Hwang, Inwoo;Cho, Sung-Woo;Ahn, Jee-Yin
    • BMB Reports
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    • v.54 no.8
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    • pp.413-418
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    • 2021
  • ErbB3-binding protein 1 (EBP1) is a multifunctional protein associated with neural development. Loss of Ebp1 leads to upregulation of the gene silencing unit suppressor of variegation 3-9 homolog 1 (Suv39H1)/DNA (cytosine 5)-methyltransferase (DNMT1). EBP1 directly binds to the promoter region of DNMT1, repressing DNA methylation, and hence, promoting neural development. In the current study, we showed that EBP1 suppresses histone methyltransferase activity of Suv39H1 by promoting ubiquitin-proteasome system (UPS)-dependent degradation of Suv39H1. In addition, we showed that EBP1 directly interacts with Suv39H1, and this interaction is required for recruiting the E3 ligase MDM2 for Suv39H1 degradation. Thus, our findings suggest that EBP1 regulates UPS-dependent degradation of Suv39H1 to govern proper heterochromatin assembly during neural development.

The use of culture systems for the study of oligodendrocyte development and injury: The erbB2 gene is required for the development of terminally differentiated spinal cord oligodendrocytes

  • Park, Song-Kyu;Kim, Hwan-Mook;Timothy Vartanian
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2002.05a
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    • pp.14-23
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    • 2002
  • The nervous system consists of two types of cells, which are neurons and glial cells. Among the glial cells, oligodendrodendrocytes and schwann cells form myelin sheaths in the central nervous system (CNS) and the peripheral nervous system (PNS), respectively. The major function of myelin in vertebrates is to insulate axonal and help action potential travel faster.(omitted)

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Auditory Model Design for Objective Audio Quality Measurement

  • Dongil Seo;Park, Se-Hyoung;Ryu, Seung-wan;Jaeho Shin
    • Proceedings of the IEEK Conference
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    • 2002.07c
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    • pp.1717-1720
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    • 2002
  • Objective quality measurement schemes that in- corporate properties of the human auditory system. The basilar membrane(BM) acts as a spectrum analyzer, spatially decomposing the signal into frequency components. Each filterbank is an implementation of the ERB, gam-machirp function. This filterbank is level-dependent asymmetric compensation filters. And for the validation of the auditory model, we calculate the CPD. Quality measurement is obtained from the result.

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Afatinib Reduces STAT6 Signaling of Host ARPE-19 Cells Infected with Toxoplasma gondii

  • Yang, Zhaoshou;Ahn, Hye-Jin;Park, Young-Hoon;Nam, Ho-Woo
    • Parasites, Hosts and Diseases
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    • v.54 no.1
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    • pp.31-38
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    • 2016
  • Specific gene expressions of host cells by spontaneous STAT6 phosphorylation are major strategy for the survival of intracellular Toxoplasma gondii against parasiticidal events through STAT1 phosphorylation by infection provoked $IFN-{\gamma}$. We determined the effects of small molecules of tyrosine kinase inhibitors (TKIs) on the growth of T. gondii and on the relationship with STAT1 and STAT6 phosphorylation in ARPE-19 cells. We counted the number of T. gondii RH tachyzoites per parasitophorous vacuolar membrane (PVM) after treatment with TKIs at 12-hr intervals for 72 hr. The change of STAT6 phosphorylation was assessed via western blot and immunofluorescence assay. Among the tested TKIs, Afatinib (pan ErbB/EGFR inhibitor, $5{\mu}M$) inhibited 98.0% of the growth of T. gondii, which was comparable to pyrimethamine ($5{\mu}M$) at 96.9% and followed by Erlotinib (ErbB1/EGFR inhibitor, $20{\mu}M$) at 33.8% and Sunitinib (PDGFR or c-Kit inhibitor, $10{\mu}M$) at 21.3%. In the early stage of the infection (2, 4, and 8 hr after T. gondii challenge), Afatinib inhibited the phosphorylation of STAT6 in western blot and immunofluorescence assay. Both JAK1 and JAK3, the upper hierarchical kinases of cytokine signaling, were strongly phosphorylated at 2 hr and then disappeared entirely after 4 hr. Some TKIs, especially the EGFR inhibitors, might play an important role in the inhibition of intracellular replication of T. gondii through the inhibition of the direct phosphorylation of STAT6 by T. gondii.

CONCOMITANT INHIBITION OF EPIDERMAL GROWTH FACTOR AND VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR TYROSINE KINASES IN ORAL SQUAMOUS CELL CARCINOMA (구강 편평상피세포암에서 상피성장인자 수용체와 혈관내피성장인자 수용체 타이로신 활성화효소의 동시 억제)

  • Park, Young-Wook;Lee, Sang-Shin
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.28 no.3
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    • pp.193-201
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    • 2006
  • Squamous cell carcinoma(SCC) of head and neck(SCCHN) is the sixth most common human malignant tumor. However, despite advances in prevention and treatment of SCC, the five-year survival rates for patients remain still low. To improve the outcome for patients with SCCHN, novel treatment strategies are needed. Overexpression of the epidermal growth factor(EGF) and activation of its receptor(EGFR) are associated with progressive growth of SCCHN. Vascular endothelial growth factor(VEGF) signaling molecules are related with neoangiogenesis and vascular metastasis of SCC. In this study, we determined the therapeutic effect of AEE788(Novartis Pharma AG, Basel, Switzerland), which is a dual inhibitor of EGFR/ErbB2 and VEGFR tyrosine kinases, on human oral SCC. At first, we screened the expression of EGFR, c-ErbB2(HER-2) and VEGFR-2 in a series of human oral SCC cell lines. And then we evaluated the effects of AEE788 on the phosphorylation of EGFR and VEGFR-2 in a oral SCC cell line expressing EGFR/HER-2 and VEGFR-2. We also evaluated the effects of AEE788 alone, or with paclitaxel(Taxol) on the oral SCC cell growth and apoptosis. As a result, all oral SCC cells expressed EGFR and VEGFR-2. Treatment of oral SCC cells with AEE788 led to dose-dependent inhibition of EGFR and VEGFR-2 phosphorylation, growth inhibition, and induction of apoptosis. Moreover, AEE788 sensitizes the cells to paclitaxel-mediated toxicity and apoptosis. These data mean EGFR and VEGFR-2 can be reliable targets for molecular therapy of oral SCC, and therefore warrant clinical use of EGFR/VEGFR inhibition in the treatment of patients with recurrent or metastatic oral SCC.