Widespread deregulation of phosphorylation-based signaling pathways in multiple myeloma cells: opportunities for therapeutic intervention

Multiple myeloma (MM) is a neoplasm of plasma cell origin that is largely confined to the bone marrow (BM). Chromosomal translocations and other genetic events are known to contribute to deregulation of signaling pathways that lead to transformation of plasma cells and progression to malignancy. However, the tumor stroma may also provide trophic support and enhance resistance to therapy. Phosphorylation of proteins on tyrosine, serine and threonine residues plays a pivotal role in cell growth and survival. Therefore, knowing the status of phosphorylation-based signaling pathways in cells may provide key insights into how cell growth and survival is promoted in tumor cells. To provide a more comprehensive molecular analysis of signaling disruptions in MM, we conducted a kinome profile comparison of normal plasma cells and MM plasma cells as well as their surrounding cells from normal BM and diseased BM. Integrated pathway analysis of the profiles obtained reveals deregulation of multiple signaling pathways in MM cells but also in surrounding bone marrow blood cells compared to their normal counterparts. The deregulated kinase activities identified herein, which include the mTOR (mammalian target of rapamycin)/p70S6K and ERK1/2 (extracellular signal-regulated kinases 1 and 2) pathways, are potential novel molecular targets in this lethal disease.     

Nanofiltration of polysaccharides from Agaricus subrufescens

A simplified submerged airlift cultivation was established for the production of biomass from Agaricus subrufescens. In this work, soluble polysaccharides extracted from fungal mycelium, fruiting bodies, and the residual culture media were concentrated by nanofiltration. Total and high molar mass polysaccharides and soluble solids were determined in the concentrate for the three extracts. Additionally, the permeate flow, the influences of temperature and pressure, and the resistance to the permeate flow during filtration were also evaluated. A yield of 5.5 g/L of biomass with 35 % glucose conversion was obtained when 0.5 g/L of initial inoculum was employed. Average specific speed of growth was 0.4/day, with biomass productivity of about 0.76 g/(L day). Nanofiltration has yielded polysaccharide increases of 85, 82, and 92 % in the extracts from fruiting bodies, mycelium, and liquid media, respectively. A reduction in the permeate flow was observed during filtration, and it was compensated by higher pressures and temperatures. The higher resistance to the permeate flux was caused by polarization due to concentration (polarized gel layer), reaching values of 88 % for the culture media. Maximal resistance caused by the membrane reached values of 40 % for the extract from the fruiting bodies. On the other hand, resistance caused by fouling was responsible for less than 3.5 %. In conclusion, nanofiltration is efficient to concentrate these functional compounds extracted from A. subrufescens and can, therefore, be applied in different biotechnological areas.     

One-pot synthesis of 2-C-glycosylated benzimidazoles from the corresponding methanal dimethyl acetals

A series of 2-glycosyl-benzimidazoles with alpha-d-arabinopyranosyl, beta-d-galactopyranosyl, beta-d-glucopyranosyl, beta-d-mannopyranosyl, and beta-l-rhamnopyranosyl configurations were obtained in 52-73% yields from the corresponding C-glycosylmethanal dimethyl acetals and o-phenylenediamine under catalysis with hydrogen chloride or a strongly acidic cation-exchange resin. Intermediate benzimidazolines were spontaneously oxidized by air to produce the final products in the one-pot procedure. The prepared compounds did not show any inhibitory effect on the growth of 12 strains of five different species of pathogenic yeasts.     

Can probability of genetic mutation be an indicator of clinical relevance?

NPM1 gene mutation evaluated on a population basis is a valuable and realistic tool to reflect the pathophysiological relevance of cancer. In a comparison of the NPM1 cDNA of human bladder cancer with its consensus sequence, we have found that a higher NPM1 sequence identity in a population is consistent with poor tumor differentiation, advanced tumor stage, and likelihood of recurrence. These data imply that "probability" of NPM1 mutation is an indicator of status of malignancy.     

Qualitative analysis of products formed during the acid catalyzed liquefaction of bagasse in ethylene glycol

Bagasse was liquefied in ethylene glycol (EG) catalyzed by sulfuric acid at 190 degrees C under atmospheric pressure. The compositions of the crude products obtained were analyzed after separating them into three fractions: a water-soluble fraction, an acetone-soluble fraction and a residue. With infrared, gel permeation chromatography and elemental analyses, the residue mainly included undissolved cellulose and lignin derivatives and the acetone-soluble fraction mainly contained lignin degradation products with high molecular weights. The water-soluble fraction, after further analyzed by GC-MS and HPLC, showed EG, diethylene glycol, EG derivatives, saccharides, alcohols, aldehydes, ketones, phenols, especially some acids such as formic acid, levulinic acid, acetic acid, oxalic acid and 2-hydroxy-butyric acid and their esters. The Higher Heating Value (HHV) of the residue and the acetone-soluble fractions were higher than that of bagasse. The results showed that some useful chemicals and biofuels could be obtained by this process.