RESUMO
Glioblastoma multiforme (GBM), the most aggressive and lethal primary brain tumor, is characterized by very low life expectancy. Understanding the genomic and proteogenomic characteristics of GBM is essential for devising better therapeutic approaches.Here, we performed proteomic profiling of 8 GBM and paired normal brain tissues. In parallel, comprehensive integrative genomic analysis of GBM was performed in silico using mRNA microarray and sequencing data. Two whole transcript expression profiling cohorts were used - a set of 3 normal brain tissues and 22 glioma tissue samples and a cohort of 5 normal brain tissues and 49 glioma tissue samples. A validation cohort included 529 GBM patients from The Cancer Genome Atlas datasets. We identified 36 molecules commonly changed at the level of the gene and protein, including up-regulated TGFBI and NES and down-regulated SNCA and HSPA12A. Single amino acid variant analysis identified 200 proteins with high mutation rates in GBM samples. We further identified 14 differentially expressed genes with high-level protein modification, among which NES and TNC showed differential expression at the protein level. Moreover, higher expression of NES and TNC mRNAs correlated with shorter overall survival, suggesting that these genes constitute potential biomarkers for GBM.
RESUMO
Chondroitin sulfate (ChS) was used to form polyelectrolyte complexes with chitosan (ChI), and its potential as a colon-targeted drug carrier was investigated. In order to determine the optimal conditions for the formation of a stable polyelectrolyte complex, the formation of ChS/ChI complexes was examined at two different pH values with various weight ratios, or at a fixed molar ratio of ChS/ChI of 1/2 under various pH conditions. The molar compositions of the various ChS/ChI complexes were quantitated with the use of solid-state 13C CP MAS NMR. The equivalent molar ratios of the complexes ranged from 0.47 to 0.54, in agreement with the data determined by elemental analysis. The fact that these values were close to 0.5 suggests that most of the --OSO3- and the --COO- groups on ChS formed strong electrostatic interactions with the --NH3+ groups on ChI, obeying a simple stoichiometric reaction between two oppositely charged moieties. Similar compositions of the complexes were obtained under most conditions tested; however, different strengths of the interactions between the two polysaccharides were noted from measurements of the water-associated transition and thermal degradation temperatures and the degree of ChS dissolution. FTIR and 13C NMR clearly showed H-bond formation at low pH, indicating that in addition to the varying degrees of electrostatic interaction, H bonding may be involved in complex formation. The highest degradation temperature, as determined by thermal gravimetric analysis, and the lowest ChS sol fraction, as measured by gel permeation chromatography, were observed with the complex prepared at pH 5, with a 1:1 mole ratio of the two opposite charges in feed. This complex also exhibited the highest water-associated transition temperature, as determined by differential scanning calorimetry. Furthermore, the swelling behavior of these complexes was pH dependent; this is a property that can potentially be exploited to control drug release from these complexes under specific pH conditions.
