• 제목/요약/키워드: K-Ras

검색결과 605건 처리시간 0.022초

Structure, signaling and the drug discovery of the Ras oncogene protein

  • Han, Chang Woo;Jeong, Mi Suk;Jang, Se Bok
    • BMB Reports
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    • 제50권7호
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    • pp.355-360
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    • 2017
  • Mutations in Ras GTPase are among the most common genetic alterations in human cancers. Despite extensive research investigating Ras proteins, their functions still remain a challenge over a long period of time. The currently available data suggests that solving the outstanding issues regarding Ras could lead to development of effective drugs that could have a significant impact on cancer treatment. Developing a better understanding of their biochemical properties or modes of action, along with improvements in their pharmacologic profiles, clinical design and scheduling will enable the development of more effective therapies.

Urtica Dioica and Lamium Album Decrease Glycogen Synthase Kinase-3 beta and Increase K-Ras in Diabetic Rats

  • Abedinzade, Mahmood;Rostampour, Mohammad;Mirzajani, Ebrahim;Khalesi, Zahra Bostani;Pourmirzaee, Tahere;Khanaki, Korosh
    • 대한약침학회지
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    • 제22권4호
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    • pp.248-252
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    • 2019
  • Objectives: The aim of the present work is evaluating the special effects of Urtica Dioica and Lamium Album on the serum level of K-Ras and GSK-3 beta in diabetic rats. Methods: In the present experimental study, 32 male Wistar rats randomly divided into 4 groups (Group I: normal control rats; receiving daily PBS, Group 2: diabetic control rats; receiving single dose of streptozotocin (60 mg/kg) and daily PBS, Group 3: Diabetic rats treated with 100 mg/kg of hydroalcoholic extract of the U. dioica, Group 4: Diabetic rats treated with 100 mg/kg of hydroalcoholic extract of L. Album. Diabetes-induced by an intraperitoneal injection of streptozotocin (60 mg/ kg). On the 14 th day of treatment, the weight, fasting blood sugar (FBS) and on 28 th day blood glucose, K-Ras and GSK3 beta was measured. Results: In diabetic group blood GSK- 3 beta increase in comparison to control group (P < 0.05), also blood K-Ras decrease in the diabetic group (P < 0.05). Both extracts reduced GSK-3 beta level, however, this reduction was only statistically significant by U.dioica (P < 0.05). Compared to diabetic group, blood K-Ras level increased by both extract (P < 0.05). Also diabetes induction increase blood glucose levels and both extracts decrease its level significantly (P < 0.05).there is no significant differences among both extract effects on blood glucose, and K-Ras. Conclusion: For the first time shown that both extracts by regulating GSK-3 beta and K-Ras improve blood glucose level. More studies are needed to determine all the effects of these herbs.

Design Optimization of Composite Radar Absorbing Structures to Improve Stealth Performance

  • Jang, Byungwook;Kim, Myungjun;Park, Jungsun;Lee, Sooyong
    • International Journal of Aeronautical and Space Sciences
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    • 제17권1호
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    • pp.20-28
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    • 2016
  • In this study, an efficient method of designing laminate composite radar absorbing structures (RAS) is proposed with consideration given to the structural shape so as to improve aircraft stealth performance. The calculation of the radar cross section (RCS) should be decreased to enhance the efficiency of the stochastic optimization when designing an RAS. In the proposed method, RAS are optimized to match up the input impedance of the minimal RCS, which is obtained by using physical optics and the transmission line theory. Single and double layer dielectric RAS for aircraft wings are employed as numerical examples and designed using the proposed method, RCS minimization and reflection coefficient minimization. The availability of the proposed method is assessed by comparing the similarity of the results and computation time with other design methods. According to the results, the proposed method produces the same results as the stochastic optimization, which adopts the RCS as the objective function, and can improve RAS design efficiency by reducing the number of RCS analyses.

임피던스정합을 이용한 레이더반사면적 최소화 단층형 전파흡수구조 설계 (Design of Single Layer Radar Absorbing Structures(RAS) for Minimizing Radar Cross Section(RCS) Using Impedance Matching)

  • 장병욱;박정선
    • 한국항공우주학회지
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    • 제43권2호
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    • pp.118-124
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    • 2015
  • 전파흡수구조(RAS)의 설계는 이산최적화 문제로 확률론적 최적화기법이 적용되며, 효율성을 향상시키기 위해서는 오랜 시간이 소모되는 RCS의 계산량을 감소시켜야 한다. 본 논문에서는 임피던스정합을 이용해 RCS 최소화 단층형 RAS를 설계하기 위한 효과적인 방법을 연구하였다. 연구방법에서는 물리광학법(PO)과 최적화기법의 연동을 통해 전파입사조건에 대해 대상의 RCS가 이상적으로 최소화되는 입력임피던스를 계산하였다. 다음으로 RAS의 복소유전율 및 두께는 이산최적화를 통해 계산된 입력임피던스를 최대한 만족하도록 설계되었다. 연구결과 이러한 방법은 다수의 함수계산이 필요한 확률론적 최적화기법으로 RCS를 직접 최소화한 경우와 동일한 RAS 설계치를 도출하였으며, RCS 해석의 수를 효과적으로 줄임으로써 RAS 설계를 위한 최적화에 소모되는 시간을 크게 감소시켰다.

2차원 홍수범람해석을 위한 HEC-RAS 5.0 적용성 평가 (Evaluation of an Applicability of HEC-RAS 5.0 for 2-D Flood Inundation Analysis)

  • 이춘호;이태근
    • 한국산학기술학회논문지
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    • 제17권4호
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    • pp.726-733
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    • 2016
  • 최근 집중호우로 인한 홍수발생 빈도와 그 규모가 커지고 있다. 이러한 현상을 반영하여 많은 국가에서는 향후 발생가능한 홍수로 발생할 수 있는 피해에 대한 위험성에 대한 인식을 국민에게 제고할 수 있는 홍수위험지도가 제작되고 있다. 홍수위험지도는 다양한 홍수범람해석모형을 통해 작성되는 데 침수원인에 따라 외수범람해석모형과 내수범람해석모형으로 구분할 수 있다. 국내 외적으로 다양한 홍수범람해석모형이 사용되고 있지만 미육군공병단에서 개발된 HEC-RAS 모형을 제외한 대부분은 고가의 상용 프로그램으로써 그 사용성이 제한되어 있는 것이 사실이다. 이러한 상황에서 현재 미육군공병단에서는 기존 1차원 모형인 HEC-RAS 모형과 연계 가능한 2차원 모형을 개발 중에 있다. 이 모형은 HEC-RAS 5.0이라는 명칭으로 베타버전이 공개되었다. 본 연구에서는 곡교천을 대상으로 선공개된 HEC-RAS 5.0 모형 베타버전과 국내 홍수위험지도 작성 시 사용되는 FLUMEN 모형과의 비교를 통해 모형의 특징, 사용성, 적용성, 결과의 정확성 등을 평가하였다. 본 연구를 통해 얻은 결과는 향후 HEC-RAS 5.0 모형이 안정되어 서비스 되면 외수침수범람해석과 관련된 사업과 연구 등 다방면에 활용될 수 있을 것으로 판단된다.

Ras에 의해 암화된 세포에서 dynamin-2의 발현 촉진 (Up-regulation of dynamin-2 gene expression in Ras-transformed cells)

  • 유지윤
    • 생명과학회지
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    • 제17권3호통권83호
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    • pp.375-380
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    • 2007
  • Dynamin은 여러 종류의 endocytosis 과정에서 최종적으로 endocytic vesicle을 membrane으로부터 분리하는데 중요한 역할을 하는 단백질이다. 이전의 보고에 의하면 dynamin-2는 Ras에 의해 암화된 세포에서 Ras signal의 신호 전달 단백질인 Grb2의 SH3 domain과 결합한다고 알려져 있다. 하지만 정상적인 세포 (NIH3T3)에 비해 Ras에 의해 암화된 세포 (NIH3T3(Ras))에서 이들 단백질의 발현이 높아지는지에 대해서는 아직 알려진 바가 없다. 본 연구에서는 먼저 NIH3T3 세포와 NIH3T3(Ras) 세포에서 dynamin-2와 Grb2의 단백질 발현을 보았는데, dynamin-2의 경우 NIH3T3 세포에 비해 NIH3T3(Ras) 세포에서 그 발현이 현저히 증가함을 볼 수 있었지만 Grb2의 경우 두 세포에서 발현의 차이를 관찰할 수 없었다. Competitive PCR을 이용하여 mRNA의발현정도를 확인하였을 때, 단백질 발현 정도와 마찬가지로 dynamin-2의 경우 NIH3T3(Ras) 세포에서 약 100배의 증가를 확인하였지만 Grb2의 경우 차이를 볼 수 없었다. Dynamin-2의 promoter 활성을 NIH3T3(Ras) 세포에서 관찰한 결과 start codon으로부터 300 bp에서 200 bp upstream에 dynamin-2의 promoter 활성을 조절하는 부위가 존재함을 확인할 수 있었다.

구강편평상피암종에서 상피성장인자 수용체의 과발현과 K-ras 유전자 변이 (Epidermal growth factor receptor overexpression and K-ras mutation detection in the oral squamous cell carcinoma)

  • 문병출;한세진;정동준;김경욱
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • 제37권5호
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    • pp.396-402
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    • 2011
  • Introduction: Epidermal growth factor is a single-chain polypeptide consisting of 53 amino acids with potent mitogenic activity that stimulates the proliferation of a range of normal and neoplastic cells through an interaction with its specific receptor (epidermal growth factor receptor, EGFR). This interaction plays a key role in tumor progression including the induction of tumor cell proliferation. An increased EGFR copy number have been associated with a favorable response to EGFR tyrosine kinase inhibitors therapy. In contrast, K-ras mutations tend to predict a poor response to such therapy. The aim of this study was to determine the correlation between the clinicopathological factors and the up-regulation of EGFR expression and Kras mutations in oral squamous cell carcinoma. Materials and Methods: This study examined the immunohistochemical staining of EGFR, K-ras mutation detection with peptide nucleic acid (PNA)-based real-time polymerase chain reaction (PCR) clamping in 20 specimens from 20 patients with oral squamous cell carcinoma. Results: 1. In the immunohistochemical study of poorly differentiated and invasive oral squamous cell carcinoma, a high level of EGFR staining was observed. The correlation between immunohistochemical EGFR expression and histological differentiation, as well as the tumor size of the specimens was significant (Pearson correlation analysis, significance [r] >0.5, P<0.05). 2. In PNA-based real-time PCR clamping analysis, a K-ras mutation was not detected in all specimens. Conclusion: These findings suggest that the up-regulation of the EGFR may play a role in the progression and invasion of oral squamous cell carcinoma that is, independent of a K-ras mutation.

Advances of Isomerizing-hydrogenating Properties of CoMo Catalysts Supported on ASA-Al2O3

  • Avdeenko, E.A.;Nadeina, K.A.;Larina, T.V.;Pakharukova, V.P.;Gerasimov, E.Yu.;Prosvirin, I.P.;Gabrienko, A.A.;Vatutina, Yu.V.;Klimov, O.V.;Noskov, A.S.
    • 대한화학회지
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    • 제66권5호
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    • pp.349-361
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    • 2022
  • Because hydrotreating (HDT) of FCC gasoline is one of the important processes used to prepare such gasoline for blending, the development of a catalyst for this process is of great interest. Currently, the industrial HDT of FCC gasoline consists of two stages and the creation of a new catalyst for one-stage HDT will make this process more efficient. Recently, our group has developed the CoMo/Al2O3-ASA catalyst and studied the influence of Si/Al ratio on the target reactions of HDT process. Despite the high selectivity and activity, the catalyst with ASA is not applicable in industry because of its low strength. The present work moves forward to study the influence of the ASA content in the catalyst support and clarify the possibility to develop the catalyst that combines high activity and selectivity in HDT reactions with successful performance. Here we show that the CoMo catalyst with ASA/Al2O3 molar ratio 1/1 in the support is the best combination for FCC gasoline hydrotreatment due to exceptional properties of the catalyst composition.

Cross-talk between STAT6 and Ras/MAPK Pathway for the IL-4-mediated T Cell Survival

  • So, Eui-Young;Jang, Ji-Young;Lee, Choong-Eun
    • BMB Reports
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    • 제34권6호
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    • pp.578-583
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    • 2001
  • As a prototypic Thl vs Th2 cytokine, IFN-$\gamma$ and IL-4 activate distinct STAT proteins, STAT1 and STATE, respectively. In cytokine-producing Jurkat T cells, IL-4 is effectively rescued from cell death that is induced by dexamethasone, but IFN-$\gamma$ failed to do so. Since the Ras/MAPK pathway is known to play an important role in cytokine-induced cell survival, we investigated the mechanism of T cell survival through the analysis of functional cross-talk between Ras/MAPK and distinct STAT proteins that are activated by IL-4 and IFN-$\gamma$. Although IL-4 and IFN-$\gamma$ each induced the activation of STATE and STATI. in Jurkat T cells, respectively, only IL-4 was capable of inducing MAPK. Along with tyrosine kinase inhibitors, MEK/MAPK inhibitors also caused a significant suppression of the IL-4-induced STATE activity. This suggests a positive regulation of STATE by MAPK during IL-4 signal transduction. Furthermore, transfection studies with dominant active (da) vs dominant negative (dn) Ras revealed that daRas, but not dnRas, selectively up-regulated the expression and activity of STATE with a concomitant increase in MAPK activity. These results, therefore, suggest that there is a functional cross-talk between the Ras/MAPK and Jak/STAT6 pathways, which may have a role in the IL-4-induced T cell survival.

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RAS SIGNALING IN INVASION AND MOTILITY OF MCF10A HUMAN BREAST EPITHELIAL CELLS

  • Kim, Mi-Sung;Lee, Eun-Jung;Shin, Il-Chung;Ahn, Seong-Min;Hyun Song;Kim, Hyeong-Reh-Choi;Aree Moon
    • 한국독성학회:학술대회논문집
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    • 한국독성학회 2002년도 Current Trends in Toxicological Sciences
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    • pp.76-77
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    • 2002
  • Ras expression has been suggested as a marker for tumor aggressiveness of breast cancer including the degrees of invasion and tumor recurrence. Expression of H-, K-, and N-ras is regulated in a tissue-specific manner and during development, indicating that ras proteins may have different cellular functions.(omitted)

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