Search results for "MEMBER"
showing 10 items of 491 documents
High frequency of a non-functional TAP1/LMP2 promoter polymorphism in human tumors
2002
The Tap1 and Tap2 genes encoding for a heterodimeric peptide transporter play a key role in antigen processing and presentation. The TAP complex mediates the transport of peptides generated by the IFN-gamma-inducible proteasome subunits LMP2, 7 and 10 from the cytosol into the endoplasmic reticulum (ER), where they bind to MHC class I molecules. In contrast to the frequent polymorphisms within the rat Tap genes which exert functional differences, polymorphic regions within the human Tap genes have been demonstrated, but not systematically analyzed in terms of their functional significance. Both the Tap1 and Lmp2 genes are transcribed from a bidirectional intergenic promoter which is regulat…
Role of the tumor microenvironment in the activity and expression of the p-glycoprotein in human colon carcinoma cells.
2006
The metabolic microenvironment of solid tumors is characterized by an oxygen deficiency and increased anaerobic glycolysis leading to extracellular acidosis and ATP depletion, which in turn may affect other energy-dependent cellular pathways. Since many tumors overexpress active drug transporters (e.g. the p-glycoprotein) leading to a multidrug-resistant phenotype, this study analyzes the impact of the different aspects of the extracellular microenvironment (hypoxia and acidosis) on the activity and expression of the p-glycoprotein (pGP) in the human colon carcinoma cell line LS513. For up to 24 h cells were exposed to hypoxia (pO2<0.5 mmHg), an acidic extracellular environment (pH 6.6), or…
Direct determination of intracellular daunorubicin in intact confluent monolayers of AT1 prostate carcinoma cells using a multiwell–multilabel counter
2008
The cytostatic drug daunorubicin exerts its toxic action by intercalating into the DNA. The efficacy of daunorubicin depends on the intracellular amount in the tumor cell. Here we have evaluated the use of a multiwell-multilabel reader for the direct determination of the fluorescent cytostatic drug daunorubicin in a prostate carcinoma cell line (AT1 R-3327 Dunning prostate carcinoma cells) grown on 24-well plates. We present evidence that this simple fluorescent parameter is a good measure for the toxicologically relevant amount of the drug intercalated into the DNA and, therefore, is a good predictor for the drug's cytotoxicity. The amount of cationic cytostatics in a tumor cell is primari…
Identification of new P-glycoprotein inhibitors derived from cardiotonic steroids
2014
P-glycoprotein (ABCB1, MDR1) is capable of extruding chemotherapeutics outside the cell and its overexpression in certain cancer cells may cause failure of chemotherapy. Many attempts were carried out to identify potent inhibitors of this transporter and numerous compounds were shown to exert inhibitory effects in vitro, but so far none were able to make their way to the clinic due to serious complications. Natural compounds represent a great source of therapeutics, which are believed to be safe and effective. Therefore, we have screened a large library of naturally occurring cardiotonic steroids and their derivatives using high throughput flow cytometry. We were able to identify six compou…
Herpes virus entry mediator synergizes with Toll-like receptor mediated neutrophil inflammatory responses
2006
In microbial infections polymorphnuclear neutrophils (PMN) constitute a major part of the innate host defence, based upon their ability to rapidly accumulate in inflamed tissues and clear the site of infection from microbial pathogens by their potent effector mechanisms. The recently described transmembrane receptor herpes virus entry mediator (HVEM) is a member of the tumour necrosis factor receptor super family and is expressed on many haematopoietic cells, including T cells, B cells, natural killer cells, monocytes and PMN. Interaction of HVEM with the natural ligand LIGHT on T cells has a costimulatory effect, and increases the bactericidal activity of PMN. To further characterize the f…
Multiparametric evaluation of the cytoprotective effect of the Mangifera indica L. stem bark extract and mangiferin in HepG2 cells.
2012
Abstract Objective Mango (Mangifera indica L.) stem bark extract (MSBE) is a natural product with biological properties and mangiferin is the major component. This paper reported the evaluation of the protective effects of MSBE and mangiferin against the toxicity induced in HepG2 cells by tert-butyl hydroperoxide or amiodarone. Method Nuclear morphology, cell viability, intracellular calcium concentration and reactive oxygen species (ROS) production were measured by using a high-content screening multiparametric assay. Key findings MSBE and mangiferin produced no toxicity below 500 mg/ml doses. A marked recovery in cell viability, which was reduced by the toxicants, was observed in cells pr…
Vitamin E transport, membrane incorporation and cell metabolism: Is α-tocopherol in lipid rafts an oar in the lifeboat?
2010
International audience; Vitamin E is composed of closely related compounds, including tocopherols and tocotrienols. Studies of the last decade provide strong support for a specific role of alpha-tocopherol in cell signalling and the regulation of gene expression. It produces significant effects on inflammation, cell proliferation and apoptosis that are not shared by other vitamin E isomers with similar antioxidant properties. The different behaviours of vitamin E isomers might relate, at least in part, to the specific effects they exert at the plasma membrane. alpha-Tocopherol is not randomly distributed throughout the phospholipid bilayer of biological membranes, and as compared with other…
Immunotherapy With Human Gamma Delta T Cells—Synergistic Potential of Epigenetic Drugs?
2018
Epigenetics has emerged as one of the fastest growing concepts, adding more than 45 new publications every day, spreading through various fields ( 1). Conrad Waddington coined the term “epigenetics” in 1942; however, a multitude of definitions has been endorsed by different researchers. In essence, Waddington’s definition of “epigenetics” and its redefinition by Holiday is at the heart of cellular function. Hence, it is obvious that epigenetic regulation plays a central role also in the specification, differentiation, and functional plasticity of T lymphocytes ( 2). T-cell fate decision in progenitor cells, functional CD4 T-cell plasticity, CD8 T-cell differentiation, but also T-cell memory…
Eight-membered heterocycles with two heteroatoms in a 1,3-relationship of interest in medicinal chemistry
2022
This chapter deals with 1,3-diheterocines, eight-membered heterocyclic systems with two heteroatoms, N, O and S, in a 1,3 relationship, exhibiting biological properties and exhaustively covers the literature from 2007 to the end of November 2019. The biological results of 1,3-diazocines, 1,3-oxazocines, 1,3-dioxocins and 1,3-thiazocines, that are the largest class of 1,3-diheterocines, were collected together with the few results available for 1,3-oxathiocin and 1,3-dithiocin derivatives at that time.
Comparison of Volatile Flavor Compounds Produced by Ten Strains of Penicillium camemberti Thom
1993
Abstract Volatile compounds produced by Penicillium camemberti Thom in a milk culture medium were identified using gas chromatography coupled with mass spectrometry. Volatile compounds were mainly methyl ketones and their corresponding secondary alcohols, fatty acids, and the alcohols 3-methylbutanol, 2-methylpropanol, 3-octanol, and 1-octen-3-ol. Comparison of 10 strains of P. camemberti Thom resulted in their being grouped into 6 aromatic strain groups, This grouping seems to be useful for the selection of strains for cheese making.