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1.
Anthony J. Hesketh Caroline Maloney Christopher A. Behr Morris C. Edelman Richard D. Glick Yousef Al-Abed Marc Symons Samuel Z. Soffer Bettie M. Steinberg 《PloS one》2015,10(12)
Metastatic Ewing Sarcoma carries a poor prognosis, and novel therapeutics to prevent and treat metastatic disease are greatly needed. Recent evidence demonstrates that tumor-associated macrophages in Ewing Sarcoma are associated with more advanced disease. While some macrophage phenotypes (M1) exhibit anti-tumor activity, distinct phenotypes (M2) may contribute to malignant progression and metastasis. In this study, we show that M2 macrophages promote Ewing Sarcoma invasion and extravasation, pointing to a potential target of anti-metastatic therapy. CNI-1493 is a selective inhibitor of macrophage function and has shown to be safe in clinical trials as an anti-inflammatory agent. In a xenograft mouse model of metastatic Ewing Sarcoma, CNI-1493 treatment dramatically reduces metastatic tumor burden. Furthermore, metastases in treated animals have a less invasive morphology. We show in vitro that CNI-1493 decreases M2-stimulated Ewing Sarcoma tumor cell invasion and extravasation, offering a functional mechanism through which CNI-1493 attenuates metastasis. These data indicate that CNI-1493 may be a safe and effective adjuvant agent for the prevention and treatment of metastatic Ewing Sarcoma. 相似文献
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Nonactivated papain was treated with N-bromosuccinimide at pH 4.75. The N-bromosuccinimide-modified enzyme was characterized by (1) the change in absorbance at 280 nm, (2) amino acid analysis, (3) separate chemical determinations of tryptophan and tyrosine (4) difference spectroscopy, and (5) an N-terminal residue determination. It is concluded that N-bromosuccinimide in sevenfold molar excess oxidizes one tryptophan and two to three tyrosine residues per molecule of nonactivated papain, without causing peptide chain cleavage. Kinetic studies with several substrates and competitive peptide inhibitors were performed at pH6 using the N-bromosuccinimide-modified papain. In addition, the kinetics of the modified enzyme with the substrate alpha-N-benzoyl-L-arginine ethl ester were studied in the region of pH 3.5-9.0. All substrates (and inhibitors) test, with the exception of alpha-N-benzyoyl-L-arginine p-nitroanilide, displayed approximately a two fold decrease in both kcat and Km (or Ki), relative to the native enzyme. It is concluded that the key tryptophan residue which is probably Trp-177. 相似文献
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The voltage-sensitive Na+ channel is responsible for the action potential of membrane electrical excitability in neuronal tissue. Three methods were used to demonstrate the presence of neurotoxin-responsive Na+ channels in two hybrid cell lines resulting from the fusion of excitable human neuroblastoma cells with mouse fibroblasts. Only one of the two electrically active hybrid cell lines maintained the sensitivity of the neuroblastoma parent to tetrodotoxin (TTX). The other hybrid, although electrically active, was not responsive to TTX or scorpion venom. Comparisons of the patterns of expression of membrane excitability and of chromosome complements in these human neuroblastoma cell hybrids suggest that the phenotype of membrane excitability is composed of genetically distinct elements. 相似文献
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Spontaneous asymmetric circling behavior in hemi-parkinsonism; a human equivalent of the lesioned-circling rodent behavior 总被引:2,自引:0,他引:2
When induced experimentally in rodents, hemispheric asymmetry in basal ganglia dopamine results in spontaneous asymmetric circling toward the hemisphere with the lower level of dopamine. A similar asymmetry has long been thought to exist in the brains of hemi-Parkinsonian patients. Using an electronic turn counter, we demonstrated that, like unilaterally lesioned rats, and without being aware of it, five ambulating outpatients with hemi-Parkinson's disease exhibit spontaneous rotation toward the hemisphere containing less striatal dopaminergic activity. 相似文献
8.
Surface haemagglutinating activity of Pseudomonas aeruginosa 总被引:2,自引:0,他引:2
Intact cells of several strains of Pseudomonas aeruginosa agglutinate papain-treated human erythrocytes. The agglutinating activity appears to reside in the surface layers of the bacterium-Pseudomonas surface haemagglutinin. This activity does not correlate with the existence of the internal PA-I and PA-II lectins, the presence of fimbriae or adherence to human buccal epithelial cells. Disruption of the bacterial cells by sonication abolishes their haemagglutinating activity. The intact cells of P. aeruginosa are also able to agglutinate rabbit, chicken, dog, guinea pig and sheep erythrocytes. This activity is generally higher with papain-treated erythrocytes, except those of rabbit in which lower haemagglutinating activity is observed after papain treatment. Optimal conditions for the haemagglutination are 37 degrees C and pH 6-7. Simple sugars do not inhibit, while fetuin and hydrophobic amino acids inhibit this activity. Exposure of the bacterial cells to proteolytic enzymes, EDTA or denaturating conditions abolish the haemagglutinating activity. These results indicate that the surface haemagglutinin is a protein which agglutinates red blood cells via hydrophobic interactions. 相似文献
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NIH 3T3 cells transfected with human tumor DNA lose the transformed phenotype when treated with swainsonine 总被引:2,自引:0,他引:2
R DeSantis U V Santer M C Glick 《Biochemical and biophysical research communications》1987,142(2):348-353
Phenotypic expression of transformation was inhibited by swainsonine at concentrations which affect the late stages of glycoprotein processing but not growth of cells. In the presence of swainsonine, NIH 3T3 fibroblasts transfected with human tumor DNA (al-l) no longer grew in soft agar or expressed complex type oligosaccharides characteristic of transformed cells. Thus, it appears that glycoproteins with fully processed oligosaccharides are necessary for the maintenance of the transformed phenotype in these cells. 相似文献
10.
Fatty acyl-coenzyme A is required for budding of transport vesicles from Golgi cisternae 总被引:16,自引:0,他引:16
We describe a new role for fatty acylation. Conditions were established under which vesicular transport from the cis to the medial Golgi compartment in vitro depends strongly upon the addition of a fatty acyl-coenzyme A, e.g., palmitoyl-CoA. Using an inhibitor of long-chain acyl-CoA synthetase, we demonstrate that the fatty acid has to be activated by CoA to stimulate transport. A nonhydrolyzable analog of palmitoyl-CoA competitively inhibits transport. Electron microscopy and biochemical studies show that fatty acyl-CoA is required for budding of (non-clathrin-) coated transport vesicles from Golgi cisternae and that budding is inhibited by the nonhydrolyzable analog. 相似文献