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Metastasis is the leading cause of death in cancer patients. To understand the mechanism of metastasis, an experimental metastasis assay was established using immunodeficient mice. This article delineates the procedures involved in this assay, including sample preparation, intravenous injection, and culturing cells from lung metastases. Briefly, a pre-determined number of human cancer cells were prepared in vitro and directly injected into the circulation of immunodeficient mice through their tail veins. A small number of cells survive the turbulence in the circulation and grow as metastases in internal organs, such as lung. The injected mice are dissected after a certain period. The tissue distribution of metastases is determined under a dissecting microscope. The number of metastases in a specific tissue is counted and it directly correlates with the metastatic ability of the injected cancer cells. The arisen metastases are isolated and cultured in vitro as cell lines, which often show enhanced metastatic abilities than the parental line when injected again into immunodeficient mice. These highly metastatic derivatives become useful tools for identifying genes or molecular pathways that regulate metastatic progression.Download video file.(50M, mov) 相似文献
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Sonali S. Niphadkar 《Preparative biochemistry & biotechnology》2017,47(8):804-812
An acetyl-11-keto-β-boswellic acid (AKBA) is potent anti-inflammatory agent found in Boswellia serrata oleogum resin. Adsorption characteristics of AKBA from B. serrata were studied using macroporous adsorbent resin to understand separation and adsorption mechanism of targeted molecules. Different macroporous resins were screened for adsorption and desorption of AKBA and Indion 830 was screened as it showed higher adsorption capacity. The kinetic equations were studied and results showed that the adsorption of AKBA on Indion 830 was well fitted to the pseudo first-order kinetic model. The influence of two parameters such as temperature (298, 303, and 308?K) and pH (5–8) on the adsorption process was also studied. The experimental data was further investigated using Langmuir, Freundlich, and Temkin isotherm models. It was observed that Langmuir isotherm model was found to be the best fit for AKBA adsorption by Indion 830 and highest adsorption capacity (50.34?mg/g) was obtained at temperature of 303?K. The values of thermodynamic parameters such as the change of Gibbs free energy (ΔG*), entropy (ΔS*), and enthalpy (ΔH*), indicated that the process of adsorption was spontaneous, favourable, and exothermic. 相似文献
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Dhaneshwar S Tewari K Joshi S Godbole D Ghosh P 《Chemistry and physics of lipids》2011,164(4):307-313
Prodrug approach using diglyceride as a promoiety is a promising strategy to improve bioavailability of poorly absorbed drugs and the same was explored in the present work to improve oral bioavailability of norfloxacin; a second generation fluoroquinolone antibacterial. The prodrug was synthesized by standard procedures using dipalmitine as a carrier and the structure was confirmed by spectral analysis. Higher Log P indicated improved lipophilicity. The ester linkage between norfloxacin and dipalmitine would be susceptible to hydrolysis by lipases to release the parent drug and carrier in the body. In vivo kinetic studies in rats indicated 53% release of norfloxacin in plasma at the end of 8 h. The prodrug exhibited improved pharmacological profile than the parent compound at equimolar dose that indirectly indicated improved bioavailability. 相似文献
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Emara M Royer PJ Abbas Z Sewell HF Mohamed GG Singh S Peel S Fox J Shakib F Martinez-Pomares L Ghaemmaghami AM 《The Journal of biological chemistry》2011,286(15):13033-13040
Dendritic cells are professional antigen-presenting cells that are specialized in antigen uptake and presentation. Allergy to cat has increased substantially in recent years and has been shown to be positively associated with asthma. We have recently shown that the mannose receptor (MR), a C-type lectin expressed by dendritic cells, recognizes various glycoallergens from diverse sources and is involved in promoting allergic responses to a major house dust mite allergen in vitro. Here we investigated the potential role of MR in allergic responses to Fel d 1, a major cat allergen. Fel d 1 binding to MR was confirmed by ELISA. Using blocking, gene silencing (siRNA) experiments, and MR knock-out (MR(-/-)) cells, we have demonstrated that MR plays a major role in internalization of Fel d 1 by human and mouse antigen-presenting cells. Intriguingly, unlike other glycoallergens, recognition of Fel d 1 by MR is mediated by the cysteine-rich domain, which correlates with the presence of sulfated carbohydrates in natural Fel d 1. WT and MR(-/-) mice were used to study the role of MR in allergic sensitization to Fel d 1 in vivo. MR(-/-) mice sensitized with cat dander extract and Fel d 1 produced significantly lower levels of total IgE, Fel d 1-specific-IgE and IgG1, the hallmarks of allergic response, compared with WT mice. Our data show for the first time that Fel d 1 is a novel ligand of the cysteine-rich domain of MR and that MR is likely to play a pivotal role in allergic sensitization to airborne allergens in vivo. 相似文献
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Hill RA Rudra S Peng B Roane DS Bounds JK Zhang Y Adloo A Lu T 《Bioorganic & medicinal chemistry》2003,11(9):2099-2113
We are seeking to discover potent CNS-active sulfonylureas with structural features that allow for the formation of several types of prodrugs. We report herein the syntheses of compounds comprising an initial series of hydroxyl-substituted analogues of the potent ATP-sensitive potassium channel blockers glyburide (glibenclamide) and gliquidone. Somewhat unexpectedly, several of the compounds were found to be comparably potent to glyburide as inhibitors of specific [(3)H]glyburide binding in rat brain preparations. 相似文献
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Understanding network topology through embracing the global dynamical regulation of genes in an active state space rather than traditional one-gene–one trait approach facilitates the rational drug development process. Schistosomiasis, a neglected tropical disease, has glycerophospholipids as abundant molecules present on its surface. Lack of effective clinical solutions to treat pathogens encourages us to carry out systems-level studies that could contribute to the development of an effective therapy. Development of a strategy for identifying drug targets by combined genome-scale metabolic network and essentiality analyses through in silico approaches provides tantalizing opportunity to investigate the role of protein/substrate metabolism. A genome-scale metabolic network model reconstruction represents choline–phosphate cytidyltransferase as the rate limiting enzyme and regulates the rate of phosphatidylcholine (PC) biosynthesis. The uptake of choline was regulated by choline concentration, promoting the regulation of phosphocholine synthesis. In Schistosoma, the change in developmental stage could result from the availability of choline, hampering its developmental cycle. There are no structural reports for this protein. In order to inhibit the activity of choline–phosphate cytidyltransferase (CCT), it was modeled by homology modeling using 1COZ as the template from Bacillus subtilis. The transition-state stabilization and catalytic residues were mapped as ‘HXGH’ and ‘RTEGISTT’ motif. CCT catalyzes the formation of CDP-choline from phosphocholine in which nucleotidyltransferase adds CTP to phosphocholine. The presence of phosphocholine permits the parasite to survive in an immunologically hostile environment. This feature endeavors development of an inhibitor specific for cytidyltransferase in Schistosoma. Flavonolignans were used to inhibit this activity in which hydnowightin showed the highest affinity as compared to miltefosine. 相似文献
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