排序方式: 共有122条查询结果,搜索用时 15 毫秒
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Wei J DeAngulo G Sun W Hussain SF Vasquez H Jordan J Weinberg J Wolff J Koshkina N Heimberger AB 《Cancer immunology, immunotherapy : CII》2009,58(2):259-270
Despite aggressive surgery, radiation therapy, and chemotherapy, glioblastoma multiforme (GBM) is refractory to therapy, recurs
quickly, and results in a median survival time of only 14 months. The modulation of the apoptotic receptor Fas with cytotoxic
agents could potentiate the response to therapy. However, Fas ligand (FasL) is not expressed in the brain and therefore this
Fas-inducing cell death mechanism cannot be utilized. Vaccination of patients with gliomas has shown promising responses.
In animal studies, brain tumors of vaccinated mice were infiltrated with activated T cells. Since activated immune cells express
FasL, we hypothesized that combination of immunotherapy with chemotherapy can activate Fas signaling, which could be responsible
for a synergistic or additive effect of the combination. When we treated the human glioma cell line U-87 and GBM tumor cells
isolated from patients with TPT, Fas was up regulated. Subsequent administration of soluble Fas ligand (sFasL) to treated
cells significantly increased their cell death indicating that these Fas receptors were functional. Similar effect was observed
when CD3+ T cells were used as a source of the FasL, indicating that the up regulated Fas expression on glioma cells increases their
susceptibility to cytotoxic T cell killing. This additive effect was not observed when glioma cells were pre-treated with
temozolomide, which was unable to increase Fas expression in tumor. Inhibition of FasL activity with the antagonistic antibody
Nok-1 mitigated these effects confirming that these responses were specifically mediated by the Fas-FasL interaction. Furthermore,
the CD3+ T cells co-cultured with topotecan treated U-87 and autologous GBM tumor cells showed a significant increase in expression
in IFN-γ, a key cytokine produced by activated T cells, and accordingly enhanced tumor cytotoxicity. Based on our data we
conclude that drugs, such as topotecan, which cause up regulation of Fas on glioma cells can be potentially exploited with
immunotherapy to enhance immune clearance of tumors via Fas signaling.
Jun Wei and Guillermo DeAngulo are Co-lead authors. 相似文献
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In its attempt to survive, the fungal cell can change the cell wall composition and/or structure in response to environmental stress. The molecules involved in these compensatory mechanisms are a possible target for the development of effective antifungal agents. In the thermodimorphic fungus Paracoccidioides brasiliensis Pb01, the main polymers that compose the cell wall are chitin and glucans. These polymers form a primary barrier that is responsible for the structural integrity and formation of the cell wall. In this study the behaviour of P. brasiliensis was evaluated under incubation with cell wall stressor agents such as Calcofluor White (CFW), Congo Red (CR), Sodium Dodecyl Sulphate (SDS), NaCl, KCl, and Sorbitol. Use of concentrations at which the fungus is visually sensitive to those agents helped to explain some of the adaptive mechanisms used by P. brasiliensis in response to cell wall stress. Our results show that 1,3-β-D-glucan synthase (PbFKS1), glucosamine-6-phosphate synthase (PbGFA1) and β-1,3-glucanosyltransferase (PbGEL3)as well as 1,3-β-D-glucan and N-acetylglucosamine (GlcNAc) residues in the cell wall are involved in compensatory mechanisms against cell wall damage. 相似文献
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Denise Przybylski Thore Rohwerder Hauke Harms Nadya Yaneva Roland H. Müller 《Applied microbiology and biotechnology》2013,97(20):8875-8885
2-Hydroxyisobutyryl-coenzyme A mutase, originally discovered in the context of methyl tert-butyl ether degradation in Aquincola tertiaricarbonis L108, catalyzes the isomerization of 3-hydroxybutyryl-coenzyme A (3-HB-CoA) to 2-hydroxyisobutyryl-CoA. It thus constitutes the basis for a biotechnological route from practically any renewable carbon to 2-hydroxyisobutyrate (2-HIB) via the common metabolite 3-hydroxybutyrate. At first sight, recombinant Cupriavidus necator H16 expressing the mutase seems to be well suited for such a synthesis process, as a strong overflow metabolism via (R)-3-HB-CoA is easily induced in this bacterium possessing the poly-3-hydroxybutyrate metabolism. However, the recently established stereospecificity of the mutase, dominantly preferring the (S)-enantiomer of 3-HB-CoA, calls for a closer investigation of C. necator as potential 2-HIB production strain and raised the question about the strain’s potential to yield 2-HIB from substrates directly providing (S)-3-HB-CoA. We compared two mutase-expressing C. necator H16 strains for their capability to synthesize 2-HIB from fructose and butyrate, delivering either (R)- or (S)-3-HB-CoA. Our results indicate that due to the enantiospecificity of the mutase, fructose is a weaker substrate for 2-HIB synthesis than butyrate. Production rates achieved with the PHB-negative strain H16 PHB?4 on butyrate were higher than on fructose. Using the wild-type did not significantly improve the production rates as the latter showed a 34-fold and a 5-fold lower 2-HIB synthesis rate compared to H16 PHB?4 on fructose and butyrate, respectively. Moreover, both strains showed concomitant excretion of undesired side products, such as pyruvate and 3-hydroxybutyrate, significantly decreasing the 2-HIB yield. 相似文献
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Michailova L Kussovsky V Radoucheva T Jordanova M Markova N 《FEMS microbiology letters》2007,268(1):88-97
The course of pulmonary infection in rats infected by intranasal inoculation with a Staphylococcus aureus stable protoplast L-form was studied. Blood and bronchoalveolar samples were taken on days 3, 7, 14 and 30 after challenge and were investigated by microbiological, electron-microscopic, cytochemical and cytometric methods. The electron microscopic data and isolation of L-form cultures from bronchoalveolar samples at all experimental times demonstrated the ability of S. aureus L-form cells to internalize, replicate and persist in the lungs of infected rats to the end of the observation period, in contrast to the S. aureus parental form. It was found that persisting L-form evoked ineffectual phagocytose by alveolar macrophages and low but long-lasting inflammatory reaction in rats. The experimental model of pulmonary infection with S. aureus L-form suggests that the cell-wall-deficient bacterial forms may be involved in the pathogenesis of chronic and latent lung infections. 相似文献
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