Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The current study was undertaken to compare two methods for the efficiency of measuring tumor necrosis factor (TNF-alpha) in biological fluids, which is species undependent, reliable, sensitive, simple and not expensive. We have compared the MTT tetrazolium cytotoxic assay [1,2] and the 3H-thymidine (3H-TdR) incorporation cytostatic assay for measuring the anti-tumor activity of human recombinant TNF-alpha, of human colonic tissue and of supernatants of in vitro stimulated human and rat peritoneal macrophages. Two target cell-lines, namely murine myelomonocytic leukaemia WEHI-164- and L-929-transformed murine fibroblast cell-lines, were used in the MTT assay. The L-929 line was also used in the 3H-TdR assay. WEHI-164 was more sensitive than the L-929 cell-line in the MTT cytotoxic assay. Furthermore, the MTT assay was more sensitive to TNF-alpha than the 3H-TdR assay. Both methods can be used for the detection of anti-tumor activity in biological fluids but the MTT cytotoxic method has the advantage of being more sensitive and more simple.
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PMID:A comparison between two methods for measuring tumor necrosis factor in biological fluids. 831 31

Cell surface expression of leukosialin (sialophorin, CD43 antigen) on human neoplastic hematopoietic cell lines K-562, U-937, HL-60 and REH was determined with the aid of a new CD43 monoclonal antibody (Bra7G) by the immunochemical (radioimmunoprecipitation, immunoblotting) and immunocytofluorometric techniques. Interferon-gamma and TNF-alpha were utilized as the "physiological" inducers of differentiation-associated markers. The "non-physiological" inducer phorbol ester PMA induced down-regulation of leukosialin cell surface expression on immature erythroid-myeloid leukemia cell line K-562, but up-regulation of CD43 antigen on the promyelocyte leukemia cell line HL-60 and, to a lesser extent on the monocyte-like U-937 and CALLA+ ALL cell line REH. Retinoic acid down-regulated leukosialin on both U-937 monocyte-like cells and the CALLA+ ALL cell line REH. In contrast to these data, interferon-gamma, TNF-alpha, retinoic acid and 1,25(OH)2-vitamin D3 induced the up-regulation of leukosialin in a promyelocytic leukemia cell line HL-60.
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PMID:Modulation of leukosialin (sialophorin, CD43 antigen) on the cell surface of human hematopoietic cell lines induced by cytokins, retinoic acid and 1,25(OH)2-vitamin D3. 835 Sep 52

Total absence of CSF-1 in the op/op mouse leads to a profound and generalized deficiency of macrophages and to osteopetrosis subsequent to the absence of osteoclasts. These observations confirm that CSF-1 is a genuine regulator of macrophage and osteoclast formation in vivo. Further studies in affected animals have shown that the CSF-1 absence variably affects macrophage differentiation stages and different organ macrophage populations, and that functionally competent macrophages are produced in low numbers without CSF-1, presumably under the influence of GM-CSF and IL-3. The op/op mice have increased levels of both endogenous GM-CSF and IL-3, which apparently are not fully able to compensate for the absence of CSF-1. Macrophage deficiencies but not osteoclast deficiencies in the op/op mouse could be completely corrected by exogenous GM-CSF, while exogenous CSF-1 corrects both osteoclast and macrophage deficiencies, but only in those tissues which could be reached by CSF-1 from the circulation. Despite severe quantitative macrophage deficiencies, the op/op mice demonstrate normal in vivo phagocytosis and immune functions suggesting that CSF-1 dependent macrophages do not contribute significantly to those processes in vivo. On the other hand, the op/op mice demonstrate severe secondary deficiencies of TNF-alpha, IL-1 alpha, and G-CSF suggesting that major function of CSF-1 dependent macrophages is the release of monokines.
Leukemia 1993 Aug
PMID:In vivo role of macrophage growth factors as delineated using CSF-1 deficient op/op mouse. 836 Dec 13

The c-jun proto-oncogene belongs to the family of immediate early response genes and is inducible by serum growth factors and Tumor Necrosis Factor (TNF). In the present study we have addressed the role of c-jun for the mitogenic response of primary acute myelogenous leukemia (AML) blasts to TNF-alpha. Our data indicate that TNF-alpha treatment of these cells is associated with transcriptional activation of c-jun and accumulation of c-jun mRNA. In order to elucidate the role of c-jun for TNF-mediated growth stimulation, an antisense (AS) oligomer directed towards the translation initiation site of c-jun was instrumental. Uptake studies of oligonucleotides showed that incorporation of oligomers was maximal at 4 hours. Oligodeoxynucleotides remained stable in these cells for up to 24 hours. Treatment of AML blasts with the AS oligonucleotide resulted in intracellular duplex formation followed by efficient translation blockade of c-jun/AP-1. In contrast, sense (S) and none-sense (NS) oligodeoxynucleotides failed to form intracellular duplexes and also did not interfere with translation of c-jun/AP-1, suggesting specific elimination of c-jun/AP-1 by the AS oligomer. AML blasts cultured in the presence of AS to c-jun, but not of S or NS, failed to proliferatively respond to TNF-alpha stimulation. Taken together, our results indicate that activation of c-jun/AP-1 plays a pivotal role in the signaling cascade initiated by TNF which leads to a proliferative response of its target cells.
Leukemia 1993 Aug
PMID:The mitogenic response of AML blasts to tumor necrosis factor-alpha requires functional c-jun/AP-1. 836 Dec 27

Secretion of the potentially antileukaemic cytokines IFN-gamma and TNF-alpha was investigated for CD4+ and CD8+ TCR alpha beta + T-cell clones derived from 4 leukaemia patients 3-6 weeks after allogeneic BMT. We investigated cytokine secretion in response to the activation signal accessory cells+phytohaemagglutinin+Interleukin 2. All clones derived after BMT were capable of IFN-gamma and TNF-alpha secretion, and both for CD4+ (n = 96) and CD8+ (n = 8) T cells quantities of IFN-gamma and TNF-alpha were significantly correlated with one another. When comparing the overall results for posttransplant and normal T-cell clones derived from 2 bone marrow donors (n = 65), both CD4+ and CD8+ TCR alpha beta + T-cell clones showed increased IFN-gamma production, and CD4+ but not CD8+ clones showed a decreased TNF-alpha secretion. The results suggest that noncytotoxic T cells derived after allogeneic BMT can produce IFN-gamma and TNF-alpha and may thus be capable of mediating antileukaemic effects.
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PMID:IFN-gamma and TNF-alpha secretion by CD4+ and CD8+ TCR alpha beta + T-cell clones derived early after allogeneic bone marrow transplantation. 837 Apr 21

Recent investigations suggest that tumor necrosis factor (TNF)-alpha may utilize the sphingomyelin pathway for signal transduction. Signaling in this system involves hydrolysis of sphingomyelin to ceramide by action of a neutral sphingomyelinase and stimulation of a ceramide-activated protein kinase (Dressler, K. A., Mathias, S., and Kolesnick, R. N. (1992) Science 255, 1715-1718). To clarify the role of this pathway in TNF action, the present studies assessed the effect of the sphingomyelin pathway on activation of nuclear factor kappa B (NF-kappa B), an event considered integral to the transfer of the TNF message to the cell nucleus. As shown previously, TNF (1 nM) induced a marked increase in nuclear NF-kappa B binding in human leukemia (HL-60) cells within 5 min, and elevated binding was detected for as long as 1 h. Addition of a maximally effective concentration of sphingomyelinase, 0.1 units.ml-1, induced a 50% reduction in sphingomyelin content by 5 min from a basal level of 560 pmol.10(6) cells-1 and a quantitative increase in ceramide levels from 89 pmol.10(6) cells-1. Sphingomyelinase 0.1 units.ml-1 also induced an increase in nuclear NF-kappa B binding within 5 min, an effect measurable for as long as 1 h. As little as 1 x 10(-5) units.ml-1 sphingomyelinase was effective and a maximal effect occurred with 1 x 10(-3) units.ml-1. A cell-permeable ceramide analog, C8-ceramide, which mimics biologic effects of TNF-alpha, also enhanced nuclear NF-kappa B activation within minutes. In contrast, addition of a phospholipase C or a synthetic diacylglycerol (DG) analog, 1,2-dioctanoylglycerol, failed to enhance nuclear NF-kappa B binding despite large increases in cellular DG content. Further, TNF-alpha induced elevation in ceramide content by 2 min to 185% of control but did not affect DG levels. These studies provide evidence that stimulation of the sphingomyelin pathway leads to NF-kappa B activation in HL-60 cells.
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PMID:Tumor necrosis factor activation of the sphingomyelin pathway signals nuclear factor kappa B translocation in intact HL-60 cells. 837 8

The trophoblast, an epithelial cell of fetal origin that forms the physical barrier between the mother and developing conceptus, becomes a component of the host immune system during pregnancy. Of the classical immune cells, it most closely resembles the macrophage, also present in high numbers in the pregnant uterus. The macrophage and trophoblast, as cell classes, share characteristics such as phagocytosis, syncytialization, invasiveness, expression of the proteins CD4, CD14, IgG receptor (FcR), non-specific esterase, granulocyte macrophage-CSF (GM-CSF), colony stimulating factor 1 (CSF-1), interleukin-1 (IL-1), interleukin-6 (IL-6), tumour necrosis factor (TNF-alpha), transforming growth factors (TGF), platelet-alpha derived growth factor (PDGF) and receptors for these cytokines. In the uterus both cell types appear regulated by a common element, the uterine epithelium, that secretes cytokines such as CSF-1, GM-CSF, TNF alpha, TGF beta, IL-6, and leukaemia inhibitory factor (LIF) that target both macrophages and trophoblasts. The common characteristics and regulation that make teleological sense in terms of co-ordinating local uterine immunity during pregnancy may also be important in transmission of congenital diseases such as AIDS. The production by the uterine epithelium of a number of cytokines previously only associated with mononuclear phagocyte production and function predicts the existence of a similar, but broader, shared cytokine network encompassing trophoblast and the principal immune regulatory cell, the T lymphocyte.
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PMID:The trophoblast as an integral component of a macrophage-cytokine network. 843 11

Low concentrations of geranylgeranylacetone (GGA), known as an antiulcer agent (Teprenone), induces differentiation of various human myeloid leukemia cell lines. The cell lines examined in the present study were myeloblastic ML1, histiocytic U937, promyelocytic HL60, and multipotential K562. All of these cell lines were induced to differentiate by 20 microM GGA, as measured by NBT staining. Neither polyprenylacetones, with more or fewer isoprene units than the geranylgeranyl group, nor polyprenylalcohols had no differentiation-inducing activity. GGA used in combination with RA or TNF-alpha increased ML1 cell differentiation. The present results suggest that GGA may be a useful agent in differentiation therapy of leukemia.
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PMID:Geranylgeranylacetone used as an antiulcer agent is a potent inducer of differentiation of various human myeloid leukemia cell lines. 846 27

Tumour necrosis factor (TNF)-alpha exerts multiple effects on human acute myeloblastic leukaemia (AML) cells in vitro, including (1) synergistic stimulation of proliferation with interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF); (2) inhibition of granulocyte-CSF (G-CSF) and stem cell factor (SCF)-induced growth; (3) suppression of multiplication of clonogenic leukaemic cells; (4) induction of autocrine growth. Recently, two distinct TNF receptors (TNF-Rs), TNF-Rp55 and TNF-Rp75, have been identified. In this study we show that both receptors are expressed on freshly isolated AML blasts, with p75 being the predominant TNF-receptor type. This study investigates the roles of these two receptors in TNF-alpha-driven growth regulation of AML blasts in vitro. Using a receptor-specific antibody, it is shown that both receptor types participate in TNF-alpha-mediated stimulation of GM-CSF/IL-3-induced proliferation and in TNF-alpha-induced autocrine growth. In contrast, the TNF-alpha-triggered growth inhibition (antiproliferation) and the potent suppression of G-CSF- and SCF-induced proliferation exclusively result from activation of TNF-Rp55. Taken together, these results suggest that the proliferative effects of TNF-alpha on AML blasts are mediated through both p55 and p75 TNF receptors, whereas the TNF-alpha-signalled growth inhibition is exclusively transduced via TNF-Rp55.
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PMID:Expression and role in growth regulation of tumour necrosis factor receptors p55 and p75 in acute myeloblastic leukaemia cells. 856 81

The anti-tumor effects of actinomycin D (Act D) and recombinant human tumor necrosis factor (TNF)-alpha have been studied on 4 established murine tumor cell lines: MmB16 melanoma, Lewis lung (LL/2) carcinoma, L1 sarcoma and L1210 leukemia. During short-term incubation (24 hr) Act D produced dose-dependent cytostatic/cytotoxic effects against MmB16, LL/2 and L1 tumor cells but did not reduce the viability of these cells even at high concentration (10 micrograms/ml), below a threshold of 30-60%. However, L1210 leukemic cells were highly susceptible to Act D, and no viable cells were detected in cultures incubated with 1 microgram/ml of Act D. TNF-alpha alone, when used under the same culture conditions, had only a negligible effect on all cell lines tested. However, the combination of this cytokine with Act D produced synergistic cytotoxic effects against MmB16, LL/2 and L1 cells but not against L1210 leukemia cells. In an in vivo model of regional therapy in which tumor-bearing mice were treated with Act D and TNF-alpha, a correlation with in vitro results was observed. In mice bearing MmB16 melanoma, LL/2 carcinoma and L1 sarcoma, the most potent anti-tumor effects were observed in mice treated with Act D and TNF-alpha together. This treatment led to a delay of tumor growth and induced complete tumor regression in some cases. On the contrary, TNF-alpha did not enhance the effect of Act D in mice injected with L1210 leukemia cells. Our results show that TNF-alpha can potentiate the anti-tumor effects of Act D against tumors weakly susceptible to Act D and may be a useful adjuvant to chemotherapy in the local treatment of neoplasia.
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PMID:Potentiation of the anti-tumor effect of actinomycin D by tumor necrosis factor alpha in mice: correlation between in vitro and in vivo results. 862 Dec 60


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