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Journal of Applied Phycology - The effect of solar UV radiation exposure and NO3– supply on mycosporine-like amino acids (MAAs) accumulation in the carrageenan-producing red macroalga... 相似文献
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Chinnasamy N Wargo JA Yu Z Rao M Frankel TL Riley JP Hong JJ Parkhurst MR Feldman SA Schrump DS Restifo NP Robbins PF Rosenberg SA Morgan RA 《Journal of immunology (Baltimore, Md. : 1950)》2011,186(2):685-696
Adoptive immunotherapy using TCR-engineered PBLs against melanocyte differentiation Ags mediates objective tumor regression but is associated with on-target toxicity. To avoid toxicity to normal tissues, we targeted cancer testis Ag (CTA) MAGE-A3, which is widely expressed in a range of epithelial malignancies but is not expressed in most normal tissues. To generate high-avidity TCRs against MAGE-A3, we employed a transgenic mouse model that expresses the human HLA-A*0201 molecule. Mice were immunized with two HLA-A*0201-restricted peptides of MAGE-A3: 112-120 (KVAELVHFL) or MAGE-A3: 271-279 (FLWGPRALV), and T cell clones were generated. MAGE-A3-specific TCR α- and β-chains were isolated and cloned into a retroviral vector. Expression of both TCRs in human PBLs demonstrated Ag-specific reactivity against a range of melanoma and nonmelanoma tumor cells. The TCR against MAGE-A3: 112-120 was selected for further development based on superior reactivity against tumor target cells. Interestingly, peptide epitopes from MAGE-A3 and MAGE-A12 (and to a lesser extent, peptides from MAGE-A2 and MAGE-A6) were recognized by PBLs engineered to express this TCR. To further improve TCR function, single amino acid variants of the CDR3 α-chain were generated. Substitution of alanine to threonine at position 118 of the α-chain in the CDR3 region of the TCR improved its functional avidity in CD4 and CD8 cells. On the basis of these results, a clinical trial is planned in which patients bearing a variety of tumor histologies will receive autologous PBLs that have been transduced with this optimized anti-MAGE-A3 TCR. 相似文献
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Overwijk WW de Visser KE Tirion FH de Jong LA Pols TW van der Velden YU van den Boorn JG Keller AM Buurman WA Theoret MR Blom B Restifo NP Kruisbeek AM Kastelein RA Haanen JB 《Journal of immunology (Baltimore, Md. : 1950)》2006,176(9):5213-5222
The promising, but modest, clinical results of many human cancer vaccines indicate a need for vaccine adjuvants that can increase both the quantity and the quality of vaccine-induced, tumor-specific T cells. In this study we tested the immunological and antitumor effects of the proinflammatory cytokine, IL-23, in gp100 peptide vaccine therapy of established murine melanoma. Neither systemic nor local IL-23 alone had any impact on tumor growth or tumor-specific T cell numbers. Upon specific vaccination, however, systemic IL-23 greatly increased the relative and absolute numbers of vaccine-induced CD8(+) T cells and enhanced their effector function at the tumor site. Although IL-23 specifically increased IFN-gamma production by tumor-specific T cells, IFN-gamma itself was not a primary mediator of the vaccine adjuvant effect. The IL-23-induced antitumor effect and accompanying reversible weight loss were both partially mediated by TNF-alpha. In contrast, local expression of IL-23 at the tumor site maintained antitumor activity in the absence of weight loss. Under these conditions, it was also clear that enhanced effector function of vaccine-induced CD8(+) T cells, rather than increased T cell number, is a primary mechanism underlying the antitumor effect of IL-23. Collectively, these results suggest that IL-23 is a potent vaccine adjuvant for the induction of therapeutic, tumor-specific CD8(+) T cell responses. 相似文献
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Molecular and comparative genetics of mental retardation 总被引:19,自引:0,他引:19
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Fas (Apo-1/CD95) is a cell-surface protein that is responsible for initiating a cascade of proteases (caspases) culminating
in apoptotic cell death in a variety of cell types. The function of the Fas/FasL system in the dampening of immune responses
to infectious agents through the autocrine deletion of activated T cells has been well documented. More recently, it has been
proposed that tumor cells express FasL, presumably to avoid immune detection. In this review, we focus on the role of the
interaction of Fas and FasL in the modulation of antitumor responses. We critically examine the evidence that FasL is expressed
by tumor cells and explore alternative explanations for the observed phenomena in vitro and in vivo. By reviewing data that
we have generated in our laboratory as well as reports from the literature, we will argue that the Fas/FasL system is a generalized
mechanism used in an autocrine fashion to regulate cell survival and expansion in response to environmental and cellular cues.
We propose that FasL expression by tumor cells, when present, is indicative of a perturbed balance in the control of proliferation
while “immune privilege” is established by “suicide” of activated antitumor T cells, a form of activation-induced cell death.
Received: 5 May 1998 / Accepted: 20 May 1998 相似文献
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Carbohydrates have been suggested to account for some IgE cross- reactions
between various plant, insect, and mollusk extracts, while some IgG
antibodies have been successfully raised against plant glycoproteins. A rat
monoclonal antibody raised against elderberry abscission tissue (YZ1/2.23)
and rabbit polyclonal antiserum against horseradish peroxidase were
screened for reactivity in enzyme-linked immunosorbent assay against a
range of plant glycoproteins and extracts as well as neoglycoproteins, bee
venom phospholipase, and several animal glycoproteins. Of the
oligosaccharides tested, Man3XylFucGlcNAc2(MMXF3) derived from horseradish
peroxidase was the most potent inhibitor of the reactivity of both YZ1/2.23
and anti- horseradish peroxidase to native horseradish peroxidase
glycoprotein. The reactivity of YZ1/2. 23 and anti-horseradish peroxidase
against Sophora japonica lectin was most inhibited by a neoglycoconjugate
of bromelain glycopeptide cross-linked to bovine serum albumin, while the
defucosylated form of this conjugate was inactive as an inhibitor. A wide
range of plant extracts was found to react against YZ1/2.23 and
anti-horseradish peroxidase, with particularly high reactivities recorded
for grass pollen and nut extracts. All these reactivities were inhibitable
with the bromelain glycopeptide/bovine serum albumin conjugate. Bee venom
phospholipase and whole bee venom reacted weakly with YZ1/2.23 but more
strongly with anti-horseradish peroxidase in a manner inhibitable with the
bromelain glycopeptide/bovine serum albumin conjugate, while hemocyanin
from Helix pomatia reacted poorly with YZ1/2.23 but did react with
anti-horseradish peroxidase. It is concluded that the alpha1, 3-fucose
residue linked to the chitobiose core of plant glycoproteins is the most
important residue in the epitope recognized by the two antibodies studied,
but that the polyclonal anti-horseradish peroxidase antiserum also contains
antibody populations that recognize the xylose linked to the core mannose
of many plant and gastropod N-linked oligosaccharides.
相似文献
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S.N. Cherenkevich J.M. Vanderkooi R. Restifo R.P. Daniele A. Holian 《Archives of biochemistry and biophysics》1982,214(1):299-304
Time-resolved fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene was used to monitor physical changes in the membranes of guinea pig alveolar macrophages following stimulation by N-formyl peptides (either N-formylmethionylphenylalanine (FMP) or N-formyl methionyl leucylphenylalanine (FMLP)) and concanavalin A. The anisotropy of diphenylhexatriene in macrophages showed a dependence on stimulation both in the rate of decay and in the value of anisotropy at infinite time. Subtle differences were observed between the effect of concanavalin A and FMLP on the membrane lipid fluidity as detected by fluorescence anisotropy. Concanavalin A stimulation of macrophages decreased the value of the anisotropy at infinite times in the range of 0–20 °C and increased the value at 25–40 °C; and at all temperatures it decreased the rate of decay of anisotropy. At temperatures below 25 °C, the response to FMLP was similar to concanavalin A, but above 25 °C, FMLP only slightly modified the anisotropy decay profile. Another physical parameter, calcium permeability, was examined because Ca+2 fluxes are dependent upon membrane properties. The temperature-dependent profiles of concanavalin A and FMP-stimulated 45Ca+2 efflux from alveolar macrophages were similar. The rate and extent of 45Ca+2 efflux increased from 4 to 22 °C, with no further increases observed up to 37 °C. This pattern correlated well with observed changes in membrane fluidity. 相似文献