• Title/Summary/Keyword: K-RAS

Search Result 605, Processing Time 0.025 seconds

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

  • Han, Chang Woo;Jeong, Mi Suk;Jang, Se Bok
    • BMB Reports
    • /
    • v.50 no.7
    • /
    • pp.355-360
    • /
    • 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
    • Journal of Pharmacopuncture
    • /
    • v.22 no.4
    • /
    • pp.248-252
    • /
    • 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
    • /
    • v.17 no.1
    • /
    • pp.20-28
    • /
    • 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.

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

  • Jang, Byung-Wook;Park, Jung-Sun
    • Journal of the Korean Society for Aeronautical & Space Sciences
    • /
    • v.43 no.2
    • /
    • pp.118-124
    • /
    • 2015
  • The design of radar absorbing structures(RAS) is a discrete optimization problem and is usually processed by stochastic optimization methods. The calculation of radar cross section(RCS) should be decreased to improve the efficiency of designing RAS. In this paper, an efficient method using impedance matching is studied to design RAS for minimizing RCS. Input impedance of the minimal RCS for the specified wave incident conditions is obtained by interlocking physical optics(PO) and optimizations. Complex permittivity and thickness of RAS are designed to satisfy the calculated input impedance by a discrete optimization. The results reveal that the studied method attains the same results as stochastic optimization which have to conduct numerous RCS analysis. The efficiency of designing RAS can be enhanced by reducing the calculation of RCS.

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

  • Lee, Choon-Ho;Lee, Tae-Geun
    • Journal of the Korea Academia-Industrial cooperation Society
    • /
    • v.17 no.4
    • /
    • pp.726-733
    • /
    • 2016
  • Recently, the flood frequency and magnitude have increased due to heavy rainfall. Considering the present condition, a flood risk map has been published in many countries to raise awareness about flood damage to people. A flood inundation analysis model, which is used to publish the flood risk map, can be classified as river and inland inundation models according to the inundation cause. Although a variety of flood inundation analysis models are utilized both domestically and overseas, their usability is limited by the expensive price, except for the HEC-RAS model developed by U.S. Army Corps of Engineers (USACE). In the situation, the USACE has developed a 2-D HEC-RAS model that can be linked to the existing 1-D model. This model has been released as a beta version under the name, HEC-RAS 5.0. In this study, the HEC-RAS 5.0 model's features, usability, applicability, and accuracy were evaluated by comparing the performances on Gokgyo-cheon with the FLUMEN model, which is used for domestic flood risk mapping. The results of this study will contribute to river inundation analysis in many different ways after the HEC-RAS 5.0 model is stabilized.

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

  • Moon, Byeong-Chool;Han, Se-Jin;Jeong, Dong-Jun;Kim, Kyung-Wook
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
    • /
    • v.37 no.5
    • /
    • pp.396-402
    • /
    • 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.

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

  • Yoo, Ji-Yun
    • Journal of Life Science
    • /
    • v.17 no.3 s.83
    • /
    • pp.375-380
    • /
    • 2007
  • Dynamin plays a key role in the scission event common to various types of endocytosis. It has been previously reported that the SH3 domain-mediated association of Grb2 with dynamin-2 was dominantly found in Ras transformed cells. However, whether this association results from the increased expression of dynamin-2 and Grb2 in Ras transformed cells or not is still unknown. So in this study we first analyzed the expression levels of dynamin-2 and Grb2 and found that the expression of dynamin-2 protein was dramatically increased in Ras-transformed NIH3T3 (NIH3T3(Ras)) cells. Furthermore competitive PCR data revealed that the mRNA transcripts for dynamin-2 were increased about 100-fold in NIH3T3(Ras) compared to those of NIH3T3 cells. However, the protein level and mRNA transcript of Grb2 were not changed in these two cells. We also examined promoter activity of dynamin-2 in NIH3T3(Ras) cells and suggest the existence of Ras-responsive sequence in promoter region -300 to -200.

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.
    • Journal of the Korean Chemical Society
    • /
    • v.66 no.5
    • /
    • pp.349-361
    • /
    • 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
    • /
    • v.34 no.6
    • /
    • pp.578-583
    • /
    • 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.

  • PDF

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
    • Proceedings of the Korean Society of Toxicology Conference
    • /
    • 2002.05a
    • /
    • pp.76-77
    • /
    • 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)

  • PDF