Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: KEGG:D02003 (NBT)
 1,323 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thirty-four patients with MDS or AML following MDS were studied with regard to survival, peripheral blood values and bone marrow morphology. The effects of 1,25 dihydroxyvitamin D3 (D3) on differentiation (NBT positivity) and proliferation (3H-thymidine incorporation) were studied in suspension cultures of bone marrow cells. Twelve bone marrow donors served as controls. Normal cells showed spontaneous differentiation in vitro, but only 2/12 were induced to differentiation by D3. Myelodysplastic cells did not differentiate spontaneously, but cells from 18/34 patients differentiated after incubation with D3. Normal cells showed increased proliferation, myelodysplastic cells showed a heterogeneous response and leukemic cells reacted with decreased proliferation after D3 incubation. Poor survival was associated with low platelet counts, high percentage of bone marrow blasts (BM blast %), low spontaneous in vitro proliferation and absence of hypogranulation of myeloid cells. Platelet counts and hypogranulation retained their predictive value in a multi-variate analysis. Progression to AML was predicted by a high BM blast % and low scores for erythroid and total dysplasia. In conclusion, the pattern of in vitro proliferation showed prognostic value while the pattern of vitamin D3-induced differentiation failed to correlate to other parameters. An estimation of bone marrow dysplasia can be used to predict the development of AML. Our results add to the information about the biology of MDS and may be important for the evaluation of therapeutic trials.
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PMID:In vitro suspension culture reactions to 1,25 dihydroxyvitamin D3 in relation to bone marrow morphology and prognosis in patients with myelodysplastic syndromes. 162 79

A panel of human leukemia cell lines from various lineages (T-cell, pre B- and Non-T/Non-B cell, myelomonocytic and erythroleukemia cell lines) were utilised as model systems of the distant effects of differentiation-inducing activity (DIA) produced by the T-leukemia cell line HUT-102. DIA inhibited cell proliferation and induced distinct morphological changes which were more pronounced in the myelomonocytic and erythroleukemia cell lines than in the lymphoid cell lines. DIA triggered in the myelomonocytic and erythroleukemia cell lines an increase in the number of NBT-reducing cells and caused strong adherence to plastic surface. The T-cell lines showed aggregation of cells in floating clusters. In the isoenzyme analysis of the enzymes carboxylic esterase and acid phosphatase, it was found that DIA stimulated the new expression of isoenzymes and a stronger staining intensity of several isoenzyme bands in all cell lines, however, at varying degrees. HL-60 and HEL displayed newly a monocyte-specific isoenzyme. Several myelomonocytic and erythroleukemia cell lines were triggered to express the tartrate-resistant acid phosphatase isoenzyme. The cell kinetic, morphological, functional and isoenzymatic data demonstrated that DIA effected the development of the different blood cell types. However, it appears that the cells reached a new differentiation block after acquired expression of differentiation-linked features; the lymphoid cell lines were more limited in their response to DIA than the myeloid and erythroid cells.
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PMID:Isoenzyme studies in human leukemia-lymphoma cell lines--V. Induction of differentiation by T-cell derived differentiation-inducing activity. 349 40

Various compounds active in promoting in vitro differentiation of certain murine leukemia cell lines (Friend erythroleukemia cells and mouse myeloid leukemia cells) were tested for their capacity to induce differentiation of HL-60 cells, a human promyelocytic leukemia cell line capable of terminally differentiating in vitro to functionally mature granulocytes. Polar planar compounds including hexamethylene bisacetamide (HMBA), certain purines (particularly hypoxanthine), and actinomycin-D induced morphological and functional (as assessed by the capacity to reduce NBT dye) differentiation of HL-60. In contrast, hemin, ouabain, prostaglandin E1, X-irradiation, dexamethasone and some other anti-leukemic chemotherapeutic agents induced little if any significant differentiation of HL-60 cells. These results, together with previous observations with murine leukemia cells, suggest that the human HL-60 cells share common cellular target sites for the inducing action of polar planar compounds, hypoxanthine and actinomycin-D with some murine leukemic cells. In contrast, hemin, ouabain and prostaglandin E1 may be specific for mouse erythroleukemia cells, while X-irradiation and chemotherapeutic agents induce differentiation of both types (erythroid and myeloid) of mouse leukemic cells, but have little effect on HL-60 cells.
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PMID:Induction of morphological and functional differentiation of human promyelocytic leukemia cells (HL-60) by componuds which induce differentiation of murine leukemia cells. 615 28

Generation of superoxide may be a key step in the cytotoxicity mediated by tumour necrosis factor (TNF); cells that cannot produce oxygen radicals might be resistant to TNF. Myeloid haemopoietic cells from patients with chronic granulomatous disease (CGD) cannot produce a large burst of oxygen radicals; therefore we examined the ability of TNF to inhibit clonal growth of myeloid haemopoietic cells from patients and carriers with several types of CGD. Mononuclear light-density cells from the peripheral blood of 13 CGD patients (11 patients with defects of gp91-phox and two with p47-phox), five gp91-phox carriers and 10 normal volunteers were cultured with the appropriate growth factor and TNF in methylcellulose. As expected, TNF (0.001-100 ng/ml) inhibited colony formation of myeloid cells of normal volunteers in a dose-dependent manner. In contrast, clonal growth of myeloid cells of CGD patients was resistant to inhibition by TNF < or = 100 ng/ml. As expected, the effects of TNF on erythroid clonogenic cells, which are not capable of producing an oxygen burst, and the action of TGF-beta on clonal growth of myeloid cells, were similar in both the individuals with CGD and the normal volunteers. In X chromosome-linked female carriers of CGD (gp91-phox deficiency), TNF showed an intermediate cytotoxicity on clonal growth of myeloid cells, and analysis of NBT reduction demonstrated that the colonies derived from myeloid cells deficient in gp91-phox were resistant to TNF and those derived from the myeloid cells expressing gp91-phox were inhibited in their proliferation by TNF. This study shows for the first time that myeloid haemopoietic cells from patients with CGD are relatively resistant to the growth-inhibiting effects of high concentrations of TNF.
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PMID:Myeloid haemopoietic cells of patients with chronic granulomatous disease are relatively resistant to TNF. 780 54

Boswellic acid acetate (BC-4), a compound isolated from the herb Boswellia carterii Birdw., can induce differentiation and apoptosis of leukemia cells. Based on cell morphology and NBT reduction, BC-4 induced monocytic differentiation of myeloid leukemia HL-60, U937 and ML-1 cells at a dose under 12.5 microg/ml (24.2 microM). BC-4 was a potent inducer, with 90% of the cells showing morphologic changes and 80-90% of the cells showing NBT reduction. Specific and non-specific esterase were also increased by BC-4. Based on benzidine staining assay, BC-4 failed to induce erythroid leukemia DS-19 and K562 cells differentiation. In contrast to its selective differentiation effect, BC-4 strongly inhibited growth of all cell lines tested. The growth inhibition effect was dose- and time-dependent. In HL-60 cells, 20 microg/ml (38.8 microM) of BC-4 decreased viable cell number by 60% at 24 h, whereas at 3 days there was virtually no viable cells. Morphologic and DNA fragmentation analysis proved that BC-4 induced cell apoptosis. The dual apoptotic and differentiation effects of BC-4 suggest that it may be a powerful agent in the treatment of leukemia.
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PMID:Boswellic acid acetate induces differentiation and apoptosis in leukemia cell lines. 993 34