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  • 1
    ISSN: 1432-0584
    Keywords: Key words bcl-2 ; Ribozymes ; Programmed cell death ; Chronic myelogenous leukemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We used synthetic RNA transcripts to prove the cleavage capability of ribozymes targeted against bcl-2-related RNAs. No cleavage occurred when control oligonucliotides were used. To assess the functional role of the specific ribozymes in chronic myelogenous leukemia (CML) cell lines we cultured K562, BV173, and Daudi cells for 48 h after lipofection with 10 μM oligonucleotide. An increase in apoptotic cells, dependent on ribozyme specificity, was shown in BV173 cells.This finding was underlined by the typical morphological changes, but there is no correlation with regard to the level of bcl-2 protein expressed. Though bcl-2 appears to interfere with cell death in myeloid cells, bcl-2-targeted ribozymes do not induce programmed cell death (PCD) by reducing bcl-2 protein levels, but rather by a presently unknown mechanism.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Annals of hematology 78 (1999), S. 341-354 
    ISSN: 1432-0584
    Keywords: Key words Chemotherapy ; CML ; Radiotherapy ; Secondary leukemia ; Immunosuppression
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Treatment-related (Tr) AML and MDS after chemotherapy, radiotherapy, or the combination of both have been well characterized. However, tr-CML seems to differ from these better-known entities in frequency, clinical course, and prognosis. Tr-CML cannot be distinguished from de novo CML cytogenetically, and, in contrast to tr-AML and tr-MDS, typical chromosomal aberrations related to tr-CML have not been described. Treatment-related CML is a late effect of cytotoxic or immunosuppressive therapy which might be increasingly recognized due to a higher number of patients treated with intensive therapy regimens. We review here the available data on incidence of tr-CML as well as the affected individual's characteristics with regard to different treatment options in malignant and nonmalignant diseases.
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  • 3
    ISSN: 1432-0584
    Keywords: Key words CML ; Dendritic cell ; FISH ; FICTION
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Dendritic cells (DCs) are professional antigen-presenting cells (APCs) specialized to internalize, process, and present antigen. They have the capacity to stimulate the primary immune response of resting T-cells. We generated DCs from the adherent cell fraction of peripheral blood, as well as from purified CD34+ cells from CML patients. Characterizing DCs from ten CML patients by flow cytometry, we found that these cells are highly positive for HLA-DR, CD1a, CD23, and CD80 and negative for CD14, CD15, and CD16. The yield of DCs ranged from 19.5 to 68%. In addition, we used a functional test of FITC-dextran uptake to verify that early DCs take up large particles (0.5–3 μm) by macropinocytosis while monocytes do not. FITC-dextran uptake was detected by flow cytometry, showing that DCs had accumulated these fluorescent particles. Electron-microscopic analysis showed no major morphological differences between normal and CML-derived DCs. Furthermore, cultured DCs were isolated by FAC sorting for CD1a and HLA-DR expression. In these highly purified cells the Ph chromosome was detected by interphase fluorescence in situ hybridization (FISH) and by fluorescence immunophenotyping and interphase cytogenetics as a tool for the investigation of neoplasms (FICTION); 30–85% of DCs generated were Ph-chromosome positive. It might therefore be possible not only to prime T-cells with bcr/abl-specific synthetic peptides, but also to stimulate T cells directly with Ph-positive DCs. Use of DCs might serve as a novel therapeutic approach in CML patients, due to their ability to induce highly specific T-cell responses in an autologous system.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1365-2559
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Aims:  To carry out an immunohistochemical study on bone marrow (BM) biopsy specimens in 75 patients with chronic myelogenous leukaemia (CML) on long-term STI571 therapy.Methods and results:  Sequential BM specimens taken at intervals of 21 ± 6 months were investigated by enzyme- and immunohistochemistry including proliferating cell nuclear antigen and apoptosis. Evaluation was performed either by semiquantitative scoring or by morphometry (CD61+ megakaryopoiesis). In 41 patients with chronic phase CML, treatment resulted in a significant decrease in cellularity and neutrophil granulopoiesis contrasting with an accumulation of erythroid precursor cells. Morphometry showed a reduction of abnormal micromegakaryocytes consistent with normalization. Regression of myelofibrosis was identified in eight of 15 patients, whereas progression occurred in 17 patients; mostly in those with acceleration and blastic crisis. The increased post-treatment incidence of reactive lymphoid nodules was remarkable. Myeloblasts, CD34+ progenitors and immature myelomonocytic cells initially decreased, but recurred in 14 patients who later developed a relapse. STI571 exerted an inhibitory effect on cell proliferation associated with enhanced apoptosis in responding patients.Conclusion:  Long-term treatment with STI571 exerts pronounced changes on BM histopathology that not only involve haematopoiesis and stromal constituents, but also proliferation and apoptosis.
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