Background.Glioma is the most common form of primary malignant
brain tumor in adults, with approximately 4 cases per 100 000 people each year.
Gliomas, like many tumors, are thought to primarily metabolize glucose for energy
production; however, the reliance upon glycolysis has recently been called into
question. In this study, we aimed to identify the metabolic fuel requirements of
human glioma cells.Methods.We used database searches and tissue culture resources to
evaluate genotype and protein expression, tracked oxygen consumption rates to
study metabolic responses to various substrates, performed histochemical
techniques and fluorescence-activated cell sorting-based mitotic profiling to
study cellular proliferation rates, and employed an animal model of malignant
glioma to evaluate a new therapeutic intervention.Results.We observed the presence of enzymes required for fatty
acid oxidation within human glioma tissues. In addition, we demonstrated that this
metabolic pathway is a major contributor to aerobic respiration in
primary-cultured cells isolated from human glioma and grown under serum-free
conditions. Moreover, inhibiting fatty acid oxidation reduces proliferative
activity in these primary-cultured cells and prolongs survival in a syngeneic
mouse model of malignant glioma.Conclusions.Fatty acid oxidation enzymes are present and active within
glioma tissues. Targeting this metabolic pathway reduces energy production and
cellular proliferation in glioma cells. The drug etomoxir may provide therapeutic
benefit to patients with malignant glioma. In addition, the expression of fatty
acid oxidation enzymes may provide prognostic indicators for clinical
practice.
Increasing evidence implicates serine proteinases in the proteolytic cascades leading to the pathological destruction of extracellular matrices such as cartilage in osteoarthritis (OA). We have previously demonstrated that the type II transmembrane serine proteinase (TTSP) matriptase acts as a novel initiator of cartilage destruction via the induction and activation of matrix metalloproteinases (MMPs). Hepsin is another TTSP expressed in OA cartilage such that we hypothesized this proteinase may also contribute to matrix turnover. Herein, we demonstrate that addition of hepsin to OA cartilage in explant culture induced significant collagen and aggrecan release and activated proMMP-1 and proMMP-3. Furthermore, hepsin directly cleaved the aggrecan core protein at a novel cleavage site within the interglobular domain. Hepsin expression correlated with synovitis as well as tumour necrosis factor α expression, and was induced in cartilage by a pro-inflammatory stimulus. However, a major difference compared to matriptase was that hepsin demonstrated markedly reduced capacity to activate proteinase-activated receptor-2. Overall, our data suggest that hepsin, like matriptase, induces potent destruction of the extracellular matrix whilst displaying distinct efficiencies for the cleavage of specific substrates.
Monoclinic vanadium dioxide (VO 2 ) particles are prepared via the thermolysis of a vanadyl ethylene glycolate precursor in an atmosphere of air. Monoclinic VO 2 particles can be obtained at temperatures above 170 C in an oven. The synthetic VO 2 product exhibits high crystallinity and features a pure monoclinic phase and composition. The expected metal-insulator transition at around 68 C is revealed by differential scanning calorimetry, variable-temperature X-ray diffraction and temperature-dependent resistance curves. The exothermic decomposition of the precursor elevates the temperature of the sample and results in a final sample consisting of monoclinic VO 2 and having a high crystallinity at room temperature.
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