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Despite their well-documented immunogenicity, malignant melanomas belong to the most aggressive tumor types. A potential explanation for this is the suboptimal activation of tumor infiltrating T cells. In order to boost immune responses against tumors, a variety of treatment modalities have been tested in animal models and in clinical setting. Antigen-nonspecific approaches (e.g., IFN-alpha and IL-2), as well as active specific immunotherapeutical modalities based on the use of autologous or allogeneic tumor cell-save been investigated in clinical trials of melanoma. The identification of melanoma-associated antigens has opened new avenues in antigen-specific immunotherapy. A promising alternative for the delivery of different forms of melanoma antigens is the application of dendritic cells, the most potent antigen presenting cells capable of eliciting efficient T-cell response. Beside active immunotherapy, immune response against melanoma antigens could be increased through the adoptive transfer of tumor infiltrating lymphocytes or antigen specific T-cell clones. The most important conclusion that can be drawn from the results of published immunotherapy studies is that these modalities are able to induce durable complete tumor regressions,mostly with reasonable toxicity; however, generally only in a minority of patients. This points to the importance of appropriate patient selection, with regard to the expression of the targeted antigens and HLA molecules, as well as to the general immunocompetence of the patients. A crucial and still unsolved question is monitoring immune activation during treatment, although there are promising new tools that could prove useful in this respect. The presence of tumor-reactive CTL in the circulation or in the tumors does not guarantee an efficient immune response. It is important to assess if these T cells are in an activated and functional state. Finally, in several single target antigen-based clinical studies a therapy-induced immunoselection of antigen-negative clones, leading to disease progression, was observed. This could be overcome with the use of antigen cocktails or whole tumor approaches. A better understanding of the mechanisms of action of immunotherapeutical modalities may enhance the success rate of these strategies.  相似文献   

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Fish use the lateral line system for prey detection, predator avoidance, schooling behavior, intraspecific communication and spatial orientation. In addition the lateral line may be important for station holding and for the detection of the hydrodynamic trails (vortex streets) generated by swimming fish. We investigated the responses of anterior lateral line nerve fibers of goldfish, Carassius auratus, to unidirectional water flow (10 cm s−1) and to running water that contained a Kármán vortex street. Compared to still water conditions, both unidirectional water flow and Kármán vortex streets caused a similar increase in the discharge rate of anterior lateral line nerve fibers. If exposed to a Kármán vortex street, the amplitude of spike train frequency spectra increased at the vortex shedding frequency. This increase was especially pronounced if the fish intercepted the edge of a Kármán vortex street. Our data show that the vortex shedding frequency can be retrieved from the responses of anterior lateral line nerve fibers.  相似文献   

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Information on richness of plant resources, and their forms of use and management in the biosphere reserve Tehuacan-Cuicatlan, Mexico is analyzed. This 10 000 km2 region hosts nearly 2700 vascular plant species, and it is acknowledged as one of the arid areas with the highest floristic diversity in North America. The seven indigenous ethnic groups that live in this region have cultural roots that date back almost 10 000 years. Based upon ethnobotanical and floristic studies, as well as bibliographical sources, a total of 808 useful plant species were identified, most of them (90%) being native, and 44 species being endemic to the region. A total of 681 species are wild plants, 109 are weeds and ruderal plants, and 86 are domesticated crops. However, it was noted that considerable overlap exists between the species of these 3 categories. For example, while wild and ruderal plants (706 species) are foraged by both humans and domestic animals, 59 species of this group are also managed in situ. On the other hand, 168 wild, ruderal and domesticated species are cultivated. The Tehuacán-Cuicatlan Valley is one of the richest regions of Mexico in plant resources. Local knowledge on use and management of plants is a valuable source of information for designing conservation and social development strategies for the biosphere reserve.  相似文献   

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