sodium-dodecyl-sulfate and Brain-Neoplasms

This study is to prepare and evaluate Pluronics-modified mixed micelle (MM) to deliver polyphenolic myricetin (MYR) across the blood-brain barrier. MYR has been proven to be an effective anticancer agent against glioblastoma cells in our previous studies. However, the poor solubility of MYR limits its access to the brain. In this study, the feasibility of preparing lipid-based MM that combined sodium dodecyl sulphate (SDS) with Pluronic F68 (F68) and Labrasol was investigated. Furthermore, the nonionic surfactant coating technology for the protection of MYR against oxidation, and its attainment in oral bioavailability, was examined. On account of the altered biomaterial properties of F68/SDS-modified lipid-based micelles, myricetin-loaded mixed micelles (MYR-MMs) were prepared by solvent-evaporation method to self-assembly into MMs. The average size of MYR-MMs was 96.3 nm, with negatively charged potential and spherical in shape. The drug loading of MYR-MMs was high with the increased grafting ratio, the more prolonged drug release profile, and more effective killing glioblastoma cells in vitro. Moreover, MYR-MMs showed a higher preference for the brain than free MYR alone, suggesting the novel MMs loaded with MYR could promote absorption and increase relative bioavailability. Taken together, the F68/SDS-modified and Labrasol-modified lipid-based micelles may provide a promising method to deliver polyphenolic compounds across the brain to treat brain tumor.

Topics: Animals; Antineoplastic Agents; Brain; Brain Neoplasms; Cell Line, Tumor; Drug Carriers; Drug Delivery Systems; Flavonoids; Glioblastoma; Humans; Micelles; Poloxamer; Rats, Sprague-Dawley; Sodium Dodecyl Sulfate

Increasing attention is being paid to alterations of the hemostatic balance in tumors, in general, and brain tumors, in particular. Apparently divergent results, showing excess fibrinolysis (i.e., increased plasminogen activator activity) or its inhibition (i.e., increased inhibitor activity), have been reported. The 9L rat brain tumor is a gliosarcoma and a model used to study treatment paradigms for human gliomas. To study the roles of fibrin and fibrinolysis in this brain tumor model, we used these features to investigate the nature of the plasminogen activator (PA) and thrombin inhibitors in normal rat brain and in the 9L rat brain tumor, growing both in vitro and in vivo in rat brain. The results indicate that cells cultured from the tumor in vitro express PA inhibitory activity which is both of the protease nexin I and PA inhibitor 1 types. However, the serpin PA inhibitory activity in extracts of both the normal brain and tumor is of the protease nexin I/PA inhibitor 3 type. This activity is higher in the tumor than in the surrounding "normal" tissue. In addition, we present evidence for a novel thrombin inhibitor which (a) is present only in the tumor growing in rat brain and undetectable either in the normal brain tissue or in vitro, (b) is in a latent, but sodium dodecyl sulfate-activatable, state, and (c) does not bind urokinase. In current studies, investigators are exploring the roles of these molecules and the target serine proteases they inhibit in the pathogenesis of gliomas.

Topics: Amyloid beta-Protein Precursor; Animals; Antithrombins; Brain; Brain Neoplasms; Carrier Proteins; Cell Line; Chromatography, Affinity; Electrophoresis, Polyacrylamide Gel; Enzyme Precursors; Extracellular Matrix; Molecular Weight; Plasminogen Activators; Plasminogen Inactivators; Protease Nexins; Rats; Receptors, Cell Surface; Reference Values; Sodium Dodecyl Sulfate; Tumor Cells, Cultured; Urokinase-Type Plasminogen Activator

gamma-L-glutamyl-L-cysteinylglycine (GSH) has been shown to inactivate 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and quench DNA crosslink precursors of BCNU. Because of the central role of 2-chloroethyl-nitrosoureas in brain tumor chemotherapy, we investigated the intracellular GSH content and the expression of specific glutathione-S-transferases (GSTs) in three human malignant astrocytoma cell lines (UWR1, UWR2, and UWR3) of varying BCNU resistance to determine the interrelationship of these parameters with brain tumor BCNU resistance. GSH was assayed by ion-exchange high performance liquid chromatography after derivatization with 1-fluoro-2,4 dinitrobenzene. Both bulk and specific GST (acid, near-neutral, and basic) activities were examined using substrates that show high specificities to the different GSTs. Western blot analyses with antisera against GST-alpha, -mu, and -tau subunits were also performed on partially purified GST from the cells of each cell line. The results showed GSH content of 91, 46.5, and 28.3 nmol GSH/mg protein for UWR1, UWR2, and UWR3, respectively. Bulk GST activity (with 1-chloro-2,4-dinitrobenzene as substrate) also correlated with increasing BCNU resistance. Of the three GST classes examined by both substrate specificities and Western blotting, only the expression of the acidic form, GST-tau, correlated significantly with the rank order of BCNU resistance of the cell lines. GST-mu and -alpha were present in only trace amounts in all three cell lines.

Topics: Astrocytoma; Blotting, Western; Brain Neoplasms; Carmustine; Cisplatin; DNA, Neoplasm; Drug Resistance; Electrophoresis, Polyacrylamide Gel; Glutathione; Glutathione Disulfide; Glutathione Transferase; Humans; Sodium Dodecyl Sulfate; Substrate Specificity; Tumor Cells, Cultured

The immunoblotting technique was used to study the glycoproteins in human brain tumor samples including astrocytoma, glioblastoma, meningioma and oligodendroglioma, as well as in normal human brain. Glycoproteins were separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis, electrophoretically transferred to nitrocellulose membrane and characterized, using binding with 11 different lectins. Tumor-associated glycoproteins were found using the lectins peanut agglutinin (PNA), soybean agglutinin, Limulus polyhemus, Lotus tetragonolobus, Ricinus communis 1, (RCA-1) and wheat germ agglutinin (WGA). Their molecular masses ranged from 50 to 180 kDa. Several of them were common to the 3 types of tumors: astrocytomas, oligodendrogliomas and meningiomas. PNA, RCA-1 and WGA were the 3 most feasible lectins with regard to tumor specificity, simplicity and reproducibility.

Topics: Astrocytoma; Brain Neoplasms; Electrophoresis, Polyacrylamide Gel; Glioblastoma; Glycoproteins; Humans; Lectins; Meningioma; Molecular Weight; Neoplasm Proteins; Oligodendroglioma; Sodium Dodecyl Sulfate