• Title/Summary/Keyword: Loss of Pu

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A small molecule approach to degrade RAS with EGFR repression is a potential therapy for KRAS mutation-driven colorectal cancer resistance to cetuximab

  • Lee, Sang-Kyu;Cho, Yong-Hee;Cha, Pu-Hyeon;Yoon, Jeong-Soo;Ro, Eun Ji;Jeong, Woo-Jeong;Park, Jieun;Kim, Hyuntae;Kim, Tae Il;Min, Do Sik;Han, Gyoonhee;Choi, Kang-Yell
    • Experimental and Molecular Medicine
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    • v.50 no.11
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    • pp.12.1-12.12
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    • 2018
  • Drugs targeting the epidermal growth factor receptor (EGFR), such as cetuximab and panitumumab, have been prescribed for metastatic colorectal cancer (CRC), but patients harboring KRAS mutations are insensitive to them and do not have an alternative drug to overcome the problem. The levels of ${\beta}$-catenin, EGFR, and RAS, especially mutant KRAS, are increased in CRC patient tissues due to mutations of adenomatous polyposis coli (APC), which occur in 90% of human CRCs. The increases in these proteins by APC loss synergistically promote tumorigenesis. Therefore, we tested KYA1797K, a recently identified small molecule that degrades both ${\beta}$-catenin and Ras via $GSK3{\beta}$ activation, and its capability to suppress the cetuximab resistance of KRAS-mutated CRC cells. KYA1797K suppressed the growth of tumor xenografts induced by CRC cells as well as tumor organoids derived from CRC patients having both APC and KRAS mutations. Lowering the levels of both ${\beta}$-catenin and RAS as well as EGFR via targeting the $Wnt/{\beta}$-catenin pathway is a therapeutic strategy for controlling CRC and other types of cancer with aberrantly activated the $Wnt/{\beta}$-catenin and EGFR-RAS pathways, including those with resistance to EGFR-targeting drugs attributed to KRAS mutations.

Performance of Full Duplex Switched Ethenlet Systems with a Dual Traffic Regulator for Avionic Data Buses (이중 트래픽 조절기능이 있는 항공데이터버스용 전이중 이더넷 교환시스템의 성능 분석)

  • Kim, Seung-Hwan;Yoon, Chong-Ho;Park, Pu-Sik
    • Journal of the Institute of Electronics Engineers of Korea TC
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    • v.46 no.2
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    • pp.89-96
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    • 2009
  • As increasing the number of digital control devices installed on aircrafts and their transmission speed, various digital data buses have been introduced to provide reliable and high-speed characteristics. These characteristics of avionics data bus are highly related on the fault-tolerant performance which can make minimize jitter and loss during data transfer. In this paper, we concerned about a new traffic shaping scheme for increasing the reliability of Avionics Full Duplex Switched Ethernet (AFDX) systems based on ARINC 664 standard. We note that the conventional AFDX with a single regulator per virtual link system may produce aggregated traffics as the number of virtual links increasing. The aggregated traffic results in large jitters among frames. To remedy for the jitter and loss of data, we propose a dual regulator scheme for the AFDX system. The purpose of the additional regulator is to additionally regulate aggregated traffics from a number of per virtual link regulators. Using NS-2 simulator, we show that the proposed scheme provides a better performance than the single regulator one. It is worthwhile note that the proposed AFDX with Dual Regulator scheme can be employed to not only aircraft networks but other QoS sensitive networks for robot and industrial control systems.

HEVC Encoder Optimization using Depth Information (깊이정보를 이용한 HEVC의 인코더 고속화 방법)

  • Lee, Yoon Jin;Bae, Dong In;Park, Gwang Hoon
    • Journal of Broadcast Engineering
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    • v.19 no.5
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    • pp.640-655
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    • 2014
  • Many of today's video systems have additional depth camera to provide extra features such as 3D support. Thanks to these changes made in multimedia system, it is now much easier to obtain depth information of the video. Depth information can be used in various areas such as object classification, background area recognition, and so on. With depth information, we can achieve even higher coding efficiency compared to only using conventional method. Thus, in this paper, we propose the 2D video coding algorithm which uses depth information on top of the next generation 2D video codec HEVC. Background area can be recognized with depth information and by performing HEVC with it, coding complexity can be reduced. If current CU is background area, we propose the following three methods, 1) Earlier stop split structure of CU with PU SKIP mode, 2) Limiting split structure of CU with CU information in temporal position, 3) Limiting the range of motion searching. We implement our proposal using HEVC HM 12.0 reference software. With these methods results shows that encoding complexity is reduced more than 40% with only 0.5% BD-Bitrate loss. Especially, in case of video acquired through the Kinect developed by Microsoft Corp., encoding complexity is reduced by max 53% without a loss of quality. So, it is expected that these techniques can apply real-time online communication, mobile or handheld video service and so on.

miRNA-183 Suppresses Apoptosis and Promotes Proliferation in Esophageal Cancer by Targeting PDCD4

  • Yang, Miao;Liu, Ran;Li, Xiajun;Liao, Juan;Pu, Yuepu;Pan, Enchun;Yin, Lihong;Wang, Yi
    • Molecules and Cells
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    • v.37 no.12
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    • pp.873-880
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    • 2014
  • In our previous study, miRNA-183, a miRNA in the miR-96-182-183 cluster, was significantly over-expressed in esophageal squamous cell carcinoma (ESCC). In the present study, we explored the oncogenic roles of miR-183 in ESCC by gain and loss of function analysis in an esophageal cancer cell line (EC9706). Genome-wide mRNA micro-array was applied to determine the genes that were regulated directly or indirectly by miR-183. 3'UTR luciferase reporter assay, RT-PCR, and Western blot were conducted to verify the target gene of miR-183. Cell culture results showed that miR-183 inhibited apoptosis (p < 0.05), enhanced cell proliferation (p < 0.05), and accelerated G1/S transition (p < 0.05). Moreover, the inhibitory effect of miR-183 on apoptosis was rescued when miR-183 was suppressed via miR-183 inhibitor (p < 0.05). Western blot analysis showed that the expression of programmed cell death 4 (PDCD4), which was predicted as the target gene of miR-183 by microarray profiling and bioinformatics predictions, decreased when miR-183 was over-expressed. The 3'UTR luciferase reporter assay confirmed that miR-183 directly regulated PDCD4 by binding to sequences in the 3'UTR of PDCD4. Pearson correlation analysis further confirmed the significant negative correlation between miR-183 and PDCD4 in both cell lines and in ESCC patients. Our data suggest that miR-183 might play an oncogenic role in ESCC by regulating PDCD4 expression.