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  • 1
    ISSN: 1600-0625
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: The rapidly increasing incidence and mortality rate of malignant melanoma, together with the lack of efficient treatment of the late stages, makes it a serious threat to public health. Innovative new treatments are needed. The proteins of the ras-family of proto-oncogenes, functioning as relay switches for signalling pathways between cell surface and nucleus, are involved in cell proliferation, differentiation, apoptosis and transformation. If over-expressed or mutated they can induce and/or maintain a transformed state of a cell. Codon 61 mutations of N-ras seem to be involved in melanoma development on sun exposed sites. In order to induce an immune response towards mutated N-ras proteins we performed a phase 1 feasibility study. Ten melanoma patients were immunized intradermally 6 times with N-ras peptides (residue 49–73) with 4 codon 61 mutations using GM-CSF as adjuvant. HLA typing was not used as an inclusion criterion. Eight patients responded with strong delayed type hypersensitivity reactions. In 2 of the patients an in vitro response to the vaccine could also be detected. The specificity of the reaction could be confirmed by cloning of peptide-specific CD4 positive T cells from peripheral blood of the patients. Intradermal injection of ras peptides using GM-CSF as adjuvant is simple to perform and seems to be efficient in inducing cellular immune responses. Since a majority of the patients showed positive skin reactions and 2 of the patients analysed showed a T-helper response to this melanoma specific antigen, these promiscuous HLA class II binding mutant ras peptides may be candidates for inclusion into vaccine cocktails containing various established CTL epitopes.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    Digitale Medien
    Digitale Medien
    Springer
    Archives of dermatological research 291 (1999), S. 65-72 
    ISSN: 1432-069X
    Schlagwort(e): Key words Skin-derived lymph ; Dendritic cells ; Langerhans cells ; Dermal dendritic cells ; Lymphoid cells
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The phenotype and function of CD1a+ lymph cells is of considerable interest. By means of microsurgical lymph cannulation human lymph derived from normal skin was sampled. Cells were isolated and processed for immunocytochemistry, electron microscopy, flow cytometry and functional assays. The majority of the cells, (62%), were T cells. The other cells comprised CD1a+ cells (7%), monocytes/macrophages (8%), and B cells (1%); the remainder were erythrocytes or uncharacterized cells. The CD1a+ cells reacted with antibodies against protein S-100, HLA-DR, the Lag antigen, CD4, CD11a, CD11b, CD18, CD25, CD40, CD54, CD80 and CD86. Interestingly, a small prolow portion the of CD1a+ cells (about 5%) reacted with an antibody to CD14. The CD1a+ cells did not react with an antibody against human follicular dendritic cells nor were they CD19-, CD23-, E-cadherin- or factor XIIIa-positive. Both allogenic and antigen-specific T cell proliferation stimulated by antigen-presenting lymph cells were strongly inhibited by adding anti-CD80 and anti-CD86 antibodies. By electron microscopy Birbeck granules were detected in only 22% of the CD1a+ lymph cells and these cells exhibited an extensive ruffling of the surface. These findings demonstrate that CD1a+ lymph cells, which do not express the dermal dendritic cell marker factor XIIIa, resemble dendritic cells formerly designated as ‘veiled’ as well as lymphoid dendritic cells, suggesting that after migration to the regional lymphoid organs, Langerhans cells form a more differentiated population of dendritic cells specialized in sensitizing T lymphocytes. Our results add further support to the view that resident Langerhans cells may be precursors of lymphoid dendritic cells acquiring the final phenotype in the microenvironment of the lymph node.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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