• Title/Summary/Keyword: Mechanistic study

Search Result 298, Processing Time 0.022 seconds

LKB1/STK11 Tumor Suppressor Reduces Angiogenesis by Directly Interacting with VEGFR2 in Tumorigenesis

  • Seung Bae Rho;Hyun Jung Byun;Boh-Ram Kim;Chang Hoon Lee
    • Biomolecules & Therapeutics
    • /
    • v.31 no.4
    • /
    • pp.456-465
    • /
    • 2023
  • Cervical tumors represent a prevalent form of cancer affecting women worldwide; current treatment options involve surgery, radiotherapy, and chemotherapy. Angiogenesis, the process of new blood vessel formation, is a crucial factor in cervical tumor growth. The molecular mechanisms underlying the effects of the liver kinase B1 (LKB1/STK11) tumor suppressor protein on tumor angiogenesis have not been elucidated. Therefore, we investigated the role of LKB1 in cervical tumor angiogenesis both in vitro and in vivo in this study. Our results demonstrated that LKB1 inhibited cervical tumor angiogenesis by suppressing the expression of angiogenesis-related factors such as vascular endothelial growth factor (VEGF) and hypoxia inducible factor-1α. LKB1 directly affected both carcinoma and vascular endothelial cells, resulting in a significant reduction in tumor growth and angiogenesis. Furthermore, LKB1 was found to bind to VEGF receptor 2 (VEGFR-2) and target the VEGFR-2-mediated protein kinase B/mechanistic target of rapamycin signaling pathway in endothelial cells, thereby reducing cervical tumor growth and angiogenesis. Our study provides new insights into the molecular mechanisms underlying the anti-tumor and anti-angiogenic effects of LKB1 in cervical cancer. These findings will help develop new therapeutic strategies for cervical cancer.

Effects of traffic characteristics on pavement responses at the road intersection

  • Yang, Qun;Dai, Jingwang
    • Structural Engineering and Mechanics
    • /
    • v.47 no.4
    • /
    • pp.531-544
    • /
    • 2013
  • Compared with pavement structures of ordinary road sections, pavement structures in the intersection are exposed to more complex traffic characteristics which may exacerbates pavement distresses such as fatigue-cracking, shoving, shear deformation and rutting. Based on a field survey about traffic characteristics in the intersection conducted in Shanghai China, a three dimensional dynamic finite-element model was developed for evaluating the mechanistic responses in the pavement structures under different traffic characteristics, namely uniform speed, acceleration and deceleration. The results from this study indicated that : (1) traffic characteristics have significant effects on the distributions of the maximum principal strain (MPS) and the maximum shear stress (MSS) at the pavement surface; (2) vehicle acceleration or deceleration substantially impact the MPS and MSS at pavement surface and could increase the magnitude of them by 20 percent to 260 percent; (3) in the vertical direction, with the increase of vehicle deceleration rate, the location of the MPS peak value and the MSS peak value changes from the sub-surface layer to the pavement surface.

A Study on Neural Network Modeling of Injection Molding Process Using Taguchi Method (다구찌방법을 이용한 사출성형공정의 신경회로망 모델링에 관한 연구)

  • Choe, Gi-Heung;Yu, Byeong-Gil;Hong, Tae-Min;Lee, Gyeong-Don;Jang, Nak-Yeong
    • Transactions of the Korean Society of Mechanical Engineers A
    • /
    • v.20 no.3
    • /
    • pp.765-774
    • /
    • 1996
  • Computer Integrated Manufacturing(CIM) requires models of manufacturing processes to be implemented on the computer. These models are typically used for determining optimal process control parameters or designing adaptive control systems. In spite of the progress made in the mechanistic modeling, however, empirical models derived from experimental data play a maior role in manufacturing process modeling. This paper describes the development of a meural metwork medel for injection molding. This paper describes the development of a nueral network model for injection molding process. The model uses the CAE analysis data based on Taguchi method. The developed model is, then, compared with the traditional polynomial regression model to assess the applicabilit in practice.

A Mechanistic Study on the Nucleophilic Addition Reactions of Benzylamines to the Activated Olefins

  • Oh, Hyuck-Keun
    • Bulletin of the Korean Chemical Society
    • /
    • v.29 no.6
    • /
    • pp.1195-1198
    • /
    • 2008
  • Kinetic studies of the additions of benzylamines to a noncyclic dicarbonyl group activated olefin, methyl $\alpha$-acetyl-$\beta$ -phenylacrylates (MAP), in acetonitrile at 30.0 ${^{\circ}C}$ are reported. The rates are lower than those for the cyclic dicarbonyl group activated olefins. The addition occurs in a single step with concurrent formation of the $C_\alpha$ -N and $C_\beta$ -H bonds through a four-center hydrogen bonded transition state. The kinetic isotope effects ($k_H/k_D$ > 1.0) measured with deuterated benzylamines ($XC_6H_4CH_2ND_2$) increase with a stronger electron acceptor substituent ($\delta\sigma$ X > 0) which is the same trend as those found for other dicarbonyl group activated series (1-4). The sign and magnitude of the cross-interaction constant, ρXY, is comparable to those for the normal bond formation processes in the $S_N2$ and addition reactions. The relatively low ${\Delta}H^\neq$ and large negative ${\Delta}S^\neq$ values are also consistent with the mechanism proposed.

Comparative analysis of urinary metabolites in methamphetamine self-administrated rats

  • Choi, Boyeon;Kim, Soo Phil;Jang, Choon-Gon;Yang, Chae Ha;Lee, Sooyeun
    • Analytical Science and Technology
    • /
    • v.30 no.3
    • /
    • pp.122-129
    • /
    • 2017
  • Methamphetamine addiction is a critical issue due to the lack of effective pharmacotherapy and high potential for relapse. Nevertheless, there are no distinct biomarkers for diagnosis or prognosis for methamphetamine addiction. In the present study, a rat model for methamphetamine self-administration was established and alteration of urinary metabolites by methamphetamine addiction was investigated by the targeted metabolite analysis using mass spectrometry. Rat urine samples were collected at three time points (before and after addiction and after extinction) from the methamphetamine-addicted group as well as the age-matched control group. The collected samples were prepared using AbsoluteIDQ p180 kit and analyzed using flow injection analysis (FIA) - or high performance liquid chromatography (HPLC) - tandem mass spectrometry (MS/MS). The levels of lysine, acetylornithine and methioninesulfoxide were distinctively altered depending on the status of metheamphetamine addiction or extinction. In particular, the level of acetylornithine was reversely changed from addiction to extinction, for which further studies could be useful for biomarker discovery or mechanistic studies for methamphetamine addiction.

Extracellular synthesis of silver nanoparticle by Pseudomonas hibiscicola - Mechanistic approach

  • Punjabi, Kapil;Mehta, Shraddha;Yedurkar, Snehal;Jain, Rajesh;Mukherjee, Sandeepan;Kale, Avinash;Deshpande, Sunita
    • Advances in nano research
    • /
    • v.6 no.1
    • /
    • pp.81-92
    • /
    • 2018
  • Biosynthesis of nanoparticles has acquired particular attention due to its economic feasibility, low toxicity and simplicity of the process. Extracellular synthesis of nanoparticles by bacteria and fungi has been stated to be brought about by enzymes and other reducing agents that may be secreted in the culture medium. The present study was carried out to determine the underlying mechanisms of extracellular silver nanoparticle synthesis by Pseudomonas hibiscicola isolated from the effluent of an electroplating industry in Mumbai. Synthesized nanoparticles were characterized by spectroscopy and electron microscopic techniques. Protein profiling studies were done using Sodium Dodecyl Sulphate Polyacrylamide Gel Electrophoresis (1D-SDS PAGE) and subjected to identification by Mass Spectrometry. Characterization studies revealed synthesis of 50 nm nanoparticles of well-defined morphology. Total protein content and SDS PAGE analysis revealed a reduction of total protein content in test (nanoparticles solution) samples when compared to controls (broth supernatant). 45.45% of the proteins involved in the process of nanoparticle synthesis were identified to be oxidoreductases and are thought to be involved in either reduction of metal ions or capping of synthesized nanoparticles.

Removal of Metallic Cobalt Layers by Reactive Cold Plasma

  • Kim, Yong-Soo;Jeon, Sang-Hwan;Yim, Byung-Joo;Lee, Hyo-Cheol;Jung, Jong-Heon;Kim, Kye-Nam
    • Proceedings of the Korean Radioactive Waste Society Conference
    • /
    • 2004.06a
    • /
    • pp.32-42
    • /
    • 2004
  • Recently, plasma surface-cleaning or surface-etching techniques have been focused in respect of the decontamination of spent or used nuclear parts and equipment. In this study the removal rate of metallic cobalt surface is experimentally investigated via its surface etching rate with a $CF_4-o_2$mixed gas plasma. Experimental results reveal that a mixed etchant gas with about 80% $CF_4$-20% $O_2$ (molar) gives the highest reaction rate and the rate reaches 0.06 ${\mu}m$/min at $380^{\circ}C$ and ion-assisted etching dramatically enhances the surface reaction rate. With a negative 300 V DC bias voltage applied to the substrate, the surface reaction initiation temperature lowers and the rate increases about 20 times at $350^{\circ}C$ and up to 0.43 ${\mu}m$/min at $380^{\circ}C$, respectively. Surface morphology analysis confirms the etching rate measurements. Auger spectrum analysis clearly shows the adsorption of fluorine atoms on the reacted surface. From the current experimental findings and the results discussed in previous studies, mechanistic understanding of the surface reaction, fluorination and/or fluoro-carbonylation reaction, is provided.

  • PDF

Low-Temperature Preparation of Ultrafine Fe2O3 Powder from Organometallic Precursors (유기금속 전구체로부터 초미립 $Fe_2O_3$ 분말의 저온 합성)

  • 김정수;김익범;강한철;홍양기
    • Journal of the Korean Ceramic Society
    • /
    • v.29 no.12
    • /
    • pp.942-948
    • /
    • 1992
  • Ultrafine iron oxide powder, {{{{ gamma }}-Fe2O3 and $\alpha$-Fe2O3, were prepared by the thermal decomposition of organometallic compounds. The formation process of powder includes the thermal decomposition and oxidation of the organometallic precursors, Fe(N2H3COO)2(N2H4)2 (A) and N2H5Fe(N2H3COO)3.H2O (B). The organometallic precursors, A and B, were synthesized by the reaction of ferrous ion with hydrazinocarboxylic acid, and characterized by quantitative analysis and infrared spectroscopy. The mechanistic study for the thermal decomposition was performed by DAT-TG. The iron oxide powder was obtained by the heat treatment of the precursors at 20$0^{\circ}C$ and $600^{\circ}C$ for half an hour in air. The phases of the resulting product were proved {{{{ gamma }}-Fe2O3 and $\alpha$-Fe2O3 respectively. The particle shape was equiaxial and the particle size was less than 0.1 ${\mu}{\textrm}{m}$. Magnetic properties of the {{{{ gamma }}-Fe2O3 powder obtained from A and B was 234 Oe of coercivity, 64.26 emu/g of saturation magnetization, 23.59 emu/g of remanent magnetization and 24.1 Oe, 47.27 emu/g, 3.118 emu/g respectively. The value of $\alpha$-Fe2O3 powder was 1.494 Oe, 0.4862 emu/g, 0.1832 emu/g and 1,276 Oe, 0.4854 emu/g, 0.1856 emu/g respectively.

  • PDF

Perspectives of Integrative Cancer Genomics in Next Generation Sequencing Era

  • Kwon, So-Mee;Cho, Hyun-Woo;Choi, Ji-Hye;Jee, Byul-A;Jo, Yun-A;Woo, Hyun-Goo
    • Genomics & Informatics
    • /
    • v.10 no.2
    • /
    • pp.69-73
    • /
    • 2012
  • The explosive development of genomics technologies including microarrays and next generation sequencing (NGS) has provided comprehensive maps of cancer genomes, including the expression of mRNAs and microRNAs, DNA copy numbers, sequence variations, and epigenetic changes. These genome-wide profiles of the genetic aberrations could reveal the candidates for diagnostic and/or prognostic biomarkers as well as mechanistic insights into tumor development and progression. Recent efforts to establish the huge cancer genome compendium and integrative omics analyses, so-called "integromics", have extended our understanding on the cancer genome, showing its daunting complexity and heterogeneity. However, the challenges of the structured integration, sharing, and interpretation of the big omics data still remain to be resolved. Here, we review several issues raised in cancer omics data analysis, including NGS, focusing particularly on the study design and analysis strategies. This might be helpful to understand the current trends and strategies of the rapidly evolving cancer genomics research.

Reactive Intermediates and Reaction Mechanisms in the Oxidative Metabolism of Organophosphorus Compounds (유기인계 화합물의 산화대사중 반응성 중간체와 반응기작에 관한 고찰)

  • Kim, Jeong-Han;Toia, Robert F.;Park, Chang-Kyu
    • Korean Journal of Environmental Agriculture
    • /
    • v.15 no.2
    • /
    • pp.246-261
    • /
    • 1996
  • Organophosphorus pesticides, which are an important part of synthetic pesticides in current use contain sulfur atom in their molecules and can be activated or detoxified by environmental and/or biological metabolism. Among the related metabolic reactions, oxidative processes are particularly important with their final products and the study on the reactive intermediates formed in those reactions is essential to elucidate the metabolic pathways and mechanisms and to understand the toxicological properties. This review dealt with the reactive intermediates formed in various reactions from the structural and mechanistic point of view for organophosphorus pesticides and related compounds.

  • PDF