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排序方式: 共有89条查询结果,搜索用时 15 毫秒
1.
Michael J. Herr Jayaprakash Kotha Nikolaus Hagedorn Blake Smith Lisa K. Jennings 《PloS one》2013,8(6)
Tumor cell metastasis, a process which increases the morbidity and mortality of cancer patients, is highly dependent upon matrix metalloproteinase (MMP) production. Small molecule inhibitors of MMPs have proven unsuccessful at reducing tumor cell invasion in vivo. Therefore, finding an alternative approach to regulate MMP is an important endeavor. Tetraspanins, a family of cell surface organizers, play a major role in cell signaling events and have been implicated in regulating metastasis in numerous cancer cell lines. We stably expressed tetraspanin CD9 in an invasive and metastatic human fibrosarcoma cell line (CD9-HT1080) to investigate its role in regulating tumor cell invasiveness. CD9-HT1080 cells displayed a highly invasive phenotype as demonstrated by matrigel invasion assays. Statistically significant increases in MMP-9 production and activity were attributed to CD9 expression and were not due to any changes in other key tetraspanin complex members or MMP regulators. Increased invasion of CD9-HT1080 cells was reversed upon silencing of MMP-9 using a MMP-9 specific siRNA. Furthermore, we determined that the second extracellular loop of CD9 was responsible for the upregulation of MMP-9 production and subsequent cell invasion. We demonstrated for the first time that tetraspanin CD9 controls HT1080 cell invasion via upregulation of an integral member of the MMP family, MMP-9. Collectively, our studies provide mounting evidence that altered expression of CD9 may be a novel approach to regulate tumor cell progression. 相似文献
2.
A useful synthon to approach artificial phenylalanyl peptides in a [2 + 2 + 2] cycloaddition reaction, C(alpha,alpha)-dipropargylglycine (Dprg) is examined for its conformational preferences as a constrained residue. Crystal structure analysis and preliminary NMR results establish possible preference of the residue for folded (alpha) rather than extended (beta) region of the straight phi,psi conformational space. Boc-Dprg-L-Leu-OMe (1) displays two molecular conformations within the same crystallographic asymmetric unit, with Dprg in the alpha(R) or alpha(L) conformation, participating in a type I beta-turn or an alpha(L)-alpha(R)-type fold, in which Leu(2) assumes the alpha(R) conformation stereochemically favored for an L-chiral residue. Boc-Dprg-D-Val-L-Leu-OMe (2) displays a type I' beta-turn conformation in crystal, with both Dprg(1) and D-Val(2) assuming the alpha(L) conformation stereochemically favored for a D-chiral residue, with 4 --> 1 type hydrogen bond linking L-Leu(3) NH with Boc CO. NMR analysis using temperature variation, solvent titration, and a spin probe study suggests a fully solvent-exposed nature of Dprg NH, ruling out a fully extended C(5)-type conformation for this residue, and solvent sequestered nature of L-Leu(3) NH, suggesting possibility of a beta-turn due to Dprg assuming a folded conformation. 相似文献
3.
Kotha S Halder S Damodharan L Pattabhi V 《Bioorganic & medicinal chemistry letters》2002,12(7):1113-1115
First synthesis of a macrocylic cyclophane-based unusual alpha-amino acid derivative 11 by coupling of ethyl isocyanoacetate with 1,2-bis(4-bromomethylphenyl)ethane under phase-transfer catalysis (PTC) conditions. Phosphazene base such as 2-tert-butylimino-2-diethylamino-1,3-dimethylperhydro-1,3,2-diazaphosphorine (BEMP) is useful to improve the yield of cyclophane derivative without high dilution conditions. 相似文献
4.
5.
Acquisition of microarray data is prone to systematic errors. A correction, called normalisation, must be applied to the data before further analysis is performed. With many normalisation techniques published and in use, the best way of executing this correction remains an open question. In this study, a variety of single-slide normalisation techniques, and different parameter settings for these techniques, were compared over many replicated microarray experiments. Different normalisation techniques were assessed through the distribution of the standard deviation of replicates from one biological sample across different slides. It is shown that local normalisation outperformed global normalisation, and intensity-based 'LOWESS' outperformed trimmed mean and median normalisation techniques. Overall, the top performing normalisation technique was a print-tip-based LOWESS with zero robust iterations. Lastly, we validated this evaluation methodology by examining the ability to predict oestrogen receptor-positive and -negative breast cancer samples with data that had been normalised using different techniques. 相似文献
6.
Li C Kotha S Huang CH Mason J Yakimicki D Hawkins M 《Journal of biomechanical engineering》2003,125(3):315-322
A finite element technique was developed to investigate the thermal behavior of bone cement in joint replacement procedures. Thermal tests were designed and performed to provide the parameters in a kinetic model of bone cement exothermic polymerization. The kinetic model was then coupled with an energy balance equation using a finite element formulation to predict the temperature history and polymerization development in the bone-cement-prosthesis system. Based on the temperature history, the possibility of the thermal bone necrosis was then evaluated. As a demonstration, the effect of cement mantle thickness on the thermal behavior of the system was investigated. The temperature profiles in the bone-cement-prosthesis system have shown that the thicker the cement, the higher the peak temperature in the bone. In the 7 mm thick cement case, a peak temperature of over 55 degrees C was predicted. These high temperatures occurred in a small region near the bone/cement interface. No damage was predicted in the 3 mm and 5 mm cement mantle thickness cases. Although thermal damage was predicted in the bone for the 7 mm mantle thickness case, the amount of thermal necrosis predicted was minimal. If more cement is used in the surgical procedure, more heat will be generated and the potential for thermal bone damage may rise. The systems should be carefully selected to reduce thermal tissue damage when more cement is used. The methodology developed in this paper provides a numerical tool for the quantitative simulation of the thermal behavior of bone-cement-prosthesis designs. 相似文献
7.
Poornima L. N. Kotha Priyanka Sharma Abimbola O. Kolawole Ran Yan Mahmoud S. Alghamri Trisha L. Brockman Julian Gomez-Cambronero Katherine J. D. A. Excoffon 《PLoS pathogens》2015,11(3)
Prevention of viral-induced respiratory disease begins with an understanding of the factors that increase or decrease susceptibility to viral infection. The primary receptor for most adenoviruses is the coxsackievirus and adenovirus receptor (CAR), a cell-cell adhesion protein normally localized at the basolateral surface of polarized epithelia and involved in neutrophil transepithelial migration. Recently, an alternate isoform of CAR, CAREx8, has been identified at the apical surface of polarized airway epithelia and is implicated in viral infection from the apical surface. We hypothesized that the endogenous role of CAREx8 may be to facilitate host innate immunity. We show that IL-8, a proinflammatory cytokine and a neutrophil chemoattractant, stimulates the protein expression and apical localization of CAREx8 via activation of AKT/S6K and inhibition of GSK3β. Apical CAREx8 tethers infiltrating neutrophils at the apical surface of a polarized epithelium. Moreover, neutrophils present on the apical-epithelial surface enhance adenovirus entry into the epithelium. These findings suggest that adenovirus evolved to co-opt an innate immune response pathway that stimulates the expression of its primary receptor, apical CAREx8, to allow the initial infection the intact epithelium. In addition, CAREx8 is a new target for the development of novel therapeutics for both respiratory inflammatory disease and adenoviral infection. 相似文献
8.
Differential effects of osmotic pressure on mitochondrial respiratory chain and indices of oxidative phosphorylation 总被引:1,自引:0,他引:1
Oxidative phosphorylation was critically evaluated in terms of activities which are sensitive and insensitive to variations in external osmotic pressure in mitochondria. Integrity of mitochondria was determined in terms of a variety of parameters, including the latency of the occluded enzymes, by careful titrations as a function of external osmotic pressure as well as detergent concentrations. The evidence indicated that the rate-limiting step in respiratory states 2 and 4 would be osmotically insensitive, as opposed to the osmotically sensitive respiration of states 1 and 3 and uncoupler-stimulated respiration with glutamate + malate and succinate. Cytochrome oxidase activity in mitochondria as well as in purified reconstituted systems exhibited osmotic insensitivity but marked sensitivity to ionic strength, offering an interesting model to study the osmotically insensitive respiration. Cytochrome oxidase activity led to permeation of mannitol across the mitochondrial inner membrane. Stimulation of cytochrome oxidase activity by uncouplers did not require an intact membrane. 相似文献
9.
Summary. Two synthetic routes to bis-armed-α-amino acid derivatives are described. The first route involves alkylation of dibromo derivatives
with ethyl isocyanoacetate under phase-transfer catalysis (PTC) conditions. The second route uses a palladium-mediated Suzuki–Miyaura
cross-coupling reaction between a DL-4-boronophenylalanine derivative and aromatic diiodo (or dibromo) compounds. 相似文献
10.