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)

Tumor necrosis factor (TNF) possesses both beneficial and toxic bioactivities. Mechanisms may operate to counteract harmful effects. We have identified a TNF binding protein (TNF-BP), which shows increased levels in serum and urine of patients on regular hemodialysis treatment (RDT). TNF-BP inhibited the specific binding of human recombinant TNF (rTNF) to its cell surface receptor. Results from gel chromatography demonstrated the presence in serum and urine of a macromolecule with an apparent molecular weight of 50,000, which formed a complex with rTNF. A 62-fold purification of TNF-BP from urine of patients on RDT was achieved by ion exchange chromatography and gel chromatography. Partially purified TNF-BP reduced the growth inhibitory effect of rTNF on a susceptible leukemia cell line. TNF-BP may act as a regulator of the biological activity of TNF and could have beneficial effects in certain inflammatory conditions.
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PMID:A tumor necrosis factor binding protein is present in human biological fluids. 285 Feb 15

Proto-oncogenes are thought to be involved in cellular differentiation and proliferation. Tumor necrosis factors (TNFs) are specific cytokines that have cytostatic and cytotoxic effects in vitro against a wide range of human tumor cells. We have previously demonstrated that recombinant TNFs (rTNFs) have an antiproliferative effect on certain human leukemic cell lines (HL-60, KBM3, KBM5) and no effect on others (K562). To study the possible role of the c-myc and c-myb oncogenes in this antiproliferative effect of TNF, we examined their expression in cell lines HL-60, KBM3, KBM5, and K562 before and after incubation with rTNF-alpha. Expression of c-myc and c-myb was elevated in all cell lines prior to incubation with rTNF-alpha. In the sensitive cell lines HL-60, KBM5, and KBM3 expression of c-myc and c-myb decreased rapidly 8-, 16-, and 4-fold, respectively, by 24 hr. K562 cells, insensitive to rTNF-alpha, exhibited no change in c-myc or c-myb expression over 24 hr. These studies demonstrated that down-regulation of c-myc and c-myb expression were associated with antiproliferative effects of rTNF-alpha on these cell lines.
Leukemia 1988 Nov
PMID:Suppression of c-myc and c-myb expression in myeloid cell lines treated with recombinant tumor necrosis factor-alpha. 305 50

Tumor necrosis factor (TNF) is a soluble protein that causes damage to tumor cells but has no effect on normal cells. Human TNF was purified to apparent homogeneity as a 17.3-kilodalton protein from HL-60 leukemia cells and showed cytotoxic and cytostatic activities against various human tumor cell lines. The amino acid sequence was determined for the amino terminal end of the purified protein, and oligodeoxyribonucleotide probes were synthesized on the basis of this sequence. Complementary DNA (cDNA) encoding human TNF was cloned from induced HL-60 messenger RNA and was confirmed by hybrid-selection assay, direct expression in COS-7 cells, and nucleotide sequence analysis. The human TNF cDNA is 1585 base pairs in length and encodes a protein of 233 amino acids. The mature protein begins at residue 77, leaving a long leader sequence of 76 amino acids. Expression of high levels of human TNF in Escherichia coli was accomplished under control of the bacteriophage lambda PL promoter and gene N ribosome binding site.
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PMID:Molecular cloning of the complementary DNA for human tumor necrosis factor. 385 24

Tumor necrosis factor (TNF) and interleukin-1 (IL-1) improve the survival of lethally irradiated animals through production of hematopoietic growth factors. Exposure of fibroblasts to TNF (1000 U/ml) drastically increased granulocyte-macrophage colony-stimulating factor (GM-CSF) mRNA at 1 h and the level returned nearly to baseline by 24 h. Levels of GM-CSF RNA were less than basal level at 24 h after exposure to irradiation alone. In contrast, cells cultured with TNF (1 h) and then irradiated, had prominent expression of GM-CSF mRNA at 24 h. Transcriptional run-on analysis has shown that TNF stimulated the rate of GM-CSF transcription by > 10-fold in irradiated cells. Moreover, TNF stabilized GM-CSF mRNA at 24 h after irradiation; 4 increased from < 20 min in untreated cells to > 2 h in cells cultured initially with TNF and followed by irradiation. We repeated the same experiments with IL-1 and found that IL-1 had the same effects on accumulation, transcription, and stabilization of GM-CSF RNA. Our findings indicate that TNF and IL-1 synergize with irradiation in expression of GM-CSF gene in human fibroblasts; this increased expression occurs by enhancement of transcriptional rate and post-transcriptional stabilization of GM-CSF mRNA.
Leukemia 1995 Jul
PMID:Tumor necrosis factor and interleukin-1 synergize with irradiation in expression of GM-CSF gene in human fibroblasts. 763 Feb 3

Tumor necrosis factor (TNF) is a cytokine with pleiotropic biological activity. We have undertaken the present study to evaluate a possible ability of peripheral blood cells of healthy subjects and patients with acute monocytic leukemia to produce TNF alpha. We studied 17 leukemia patients and 8 control subjects. Spontaneous production of TNF alpha induced by LPS and Newcastle disease virus (NDV) were determined in blood cell cultures. Leukemic cells released markedly higher level of TNF alpha than control cells cultured in vitro in contrast to control cells producing TNF spontaneously. It seems that leukemic cells can produce TNF in response to very small amount of LPS; however, we cannot exclude that spontaneous TNF may be involved in autocrine regulation of proliferation and differentiation of bone marrow monocyte precursors.
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PMID:[Spontaneous and induced production of tumor necrosis factor (TNF alpha) by peripheral blood leukocytes in patients with acute leukemia type M 4 and M5 according to FAB]. 765 27

Endotoxin (lipopolysaccharide [LPS]) stimulates the production of cytokines, which mediate many of the metabolic effects associated with infection. In LPS-sensitive C57B1/6 mice, LPS doses as low as 0.01 micrograms per mouse decreased adipose tissue lipoprotein lipase (LPL) activity by greater than 50%. In LPS-resistant C3H/HeJ mice, which do not produce cytokines in response to LPS, doses of LPS as high as 10 micrograms per mouse did not affect LPL activity in adipose tissue. In muscle of C57Bl/6 mice, LPL activity was decreased by 27% after 10 micrograms of LPS, whereas in C3H/HeJ mice there was no effect. These results indicate that the LPS-induced decrease in both adipose and muscle LPL activity is mediated by cytokines. Tumor necrosis factor (TNF), interleukin (IL)-1, leukemia-inhibiting factor (LIF), interferon alfa, and interferon gamma all decreased adipose tissue LPL activity in intact mice. In skeletal and cardiac muscle, only IL-1 and interferon gamma decreased LPL activity, whereas TNF, LIF, and interferon alfa had no effect. Inhibition of TNF activity blocked the increase in serum triglycerides that is characteristically observed after LPS but did not affect the ability of LPS to decrease adipose tissue LPL activity. Inhibition of IL-1 activity with IL-1 receptor antagonist partially inhibited the increase in serum triglycerides; however, the ability of LPS to decrease LPL activity in either adipose or muscle tissue was not affected. These data indicate that although TNF and IL-1 play a role in mediating the increase in serum triglyceride levels, these cytokines do not play a crucial role in the inhibition of either adipose or muscle LPL activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of endotoxin and cytokines on lipoprotein lipase activity in mice. 794 14

Matrix metalloproteinase 9 (MMP-9), also known as 92-kD type IV collagenase/gelatinase, is believed to play a critical role in tumor invasion and metastasis. Here, we report that MMP-9 was constitutively released from the human promyelocytic cell line HL-60 as determined by zymographic analysis. Tumor necrosis factor-alpha (TNF-alpha) enhanced the enzyme release threefold to fourfold and the protein kinase C (PKC) activator and differentiation inducer 12-O-tetradecanoylphorbol-13-acetate (TPA) eightfold to ninefold. Gelatinase induction by TNF-alpha and TPA was inhibited by actinomycin D or cycloheximide, indicating that de novo protein synthesis was required. Neutralizing monoclonal antibodies to TNF-alpha (anti-TNF-alpha) decreased the basal MMP-9 release of these cells. In addition, these antibodies also significantly interfered with the TPA-induced enzyme release. Agents that inhibit TNF-alpha expression in HL-60 cells, such as pentoxifylline and dexamethasone, completely abrogated both the constitutive and TPA-evoked MMP-9 release. Diethyldithiocarbamate, which is known to stimulate TNF-alpha production in HL-60 cells, exerted a positive effect on MMP-9 release in untreated cells but was inhibitory in TPA-treated HL-60 cells. The PKC inhibitor staurosporine at low concentrations (100 ng/mL) caused a significant augmentation of MMP-9 release in untreated cultures that was blocked by the addition of anti-TNF-alpha. High concentrations (2 mumol/L) of staurosporine completely abolished the extracellular enzyme activity both in untreated and TPA-stimulated cells. These results suggest, that TNF-alpha is required for basal and PKC-mediated MMP-9 release in HL-60 leukemia cells. Thus, MMP-9 secretion may be regulated by TNF-alpha not only in a paracrine but also in an autocrine fashion. This may potentiate the matrix degradative capacity of immature leukemic cells in the processes of bone marrow egress and the evasion of these cells into peripheral tissue.
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PMID:Regulation of 92-kD gelatinase release in HL-60 leukemia cells: tumor necrosis factor-alpha as an autocrine stimulus for basal- and phorbol ester-induced secretion. 820 88

The effects of inoculation of LP-BM5 murine leukemia retrovirus and chronic ethanol (5% v/v) ingestion on immunomodulation and Cryptosporidium parvum infection in C57BL/6 female mice were evaluated. The intestinal mucosae of retrovirally immunosuppressed animals were heavily colonized by Cryptosporidium parasites, and oocysts shedding in the feces persisted throughout the duration of the study. Mortality was exacerbated by murine retrovirus infection alone and exacerbated with concomitant chronic alcohol feeding (42.8 and 69.4%). Chronic ethanol ingestion decreased production of interferon-gamma and soluble interleukin-2 receptor released in supernatants of splenocytes when stimulated with concanavalin A, compared with the control group. Decreased production of interferon-gamma and interleukin-2 receptor was further exacerbated due to retrovirus infection. Tumor necrosis factor production by splenocytes stimulated with lipopolysaccharide, however, was significantly increased because of retrovirus infection. LP-BM5 retrovirus infection alone as well as with concomitant ethanol feeding altered cytokine production, which might have led to immunodeficiency. These changes may help explain the enhanced persistence of Cryptosporidiosis.
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PMID:Alcohol and murine acquired immunodeficiency syndrome suppression of resistance to Cryptosporidium parvum infection during modulation of cytokine production. 833 81

Tumor necrosis factor-alpha (TNF-alpha) has recently been implicated as a regulator growth and differentiation of normal and malignant B cells. We utilized a selected clone (I-83) of primary resting B-type chronic lymphocytic leukemia (B-CLL) cells, inducible to activation, growth and differentiation in vitro, as a model system to study the possible role of TNF-alpha as an autocrine growth factor for such cells. Our results show that unstimulated I-83 B-CLL cells produced a low level of TNF-alpha mRNA, as shown by Northern blot analysis, and cytoplasmic TNF-alpha, determined in individual cells by immunocytochemistry. Secreted TNF-alpha could, however, not be detected in the medium by ELISA. TNF-alpha synthesis and secretion was, however, induced to high levels by stimulation of the B-CLL cells with interleukin-2 (IL-2) after activation by 12-O-tetradecanoylphorbol-13-acetate (TPA) or Staphylococcus aureus Cowan strain I (SAC) and B-cell stimulatory factor-MP6 (thioredoxin). A moderate increase in TNF-alpha secretion was also induced by TPA or IL-2 alone. IL-4 did not have any major effects on the production of TNF-alpha in activated cells, but inhibited the IL-2-induced production of TNF-alpha in SAC-activated cells. The cell surface expression of TNF-alpha receptors (TNF-R), as determined by binding assay using 125I-labelled recombinant TNF-alpha (rTNF-alpha), was also induced after SAC or TPA activation, but shed receptors (TNF-binding proteins) were only observed after TPA activation. Exogenously added rTNF-alpha in combination with TPA or SAC induced a high level of DNA synthesis in I-83 B-CLL cells. The increased endogenous production and secretion of TNF-alpha during induced growth stimulation, the induced expression of TNF-R, and the mitogenic effect of TNF-alpha on activated B-CLL cells raise the question whether TNF-alpha may function as an autocrine co-stimulator of B-CLL cell growth as recently suggested. anti-TNF-alpha and anti-TNF-R antibodies, however, failed to inhibit the IL-2- and IL-4-induced proliferation of activated I-83 B-CLL cells.
Leukemia 1993 Feb
PMID:Interleukin-2 enhances the production of tumor necrosis factor-alpha in activated B-type chronic lymphocytic leukemia (B-CLL) cells. 838 Nov 94

Tumor necrosis factor-alpha (TNF-alpha) and platelet-activating factor (PAF) have been implicated in the pathogenesis of human immunodeficiency virus (HIV)-associated encephalopathy. The effects of pentoxifylline on brain PAF levels were examined in mice infected with the LP-BM5 murine leukemia virus (MuLV). Seven weeks after viral inoculation, significant increases in serum TNF-alpha and brain PAF levels were observed. One week of treatment with pentoxifylline initiated 6 weeks postinfection significantly reduced both serum TNF-alpha and brain PAF levels. A significant positive correlation was observed between the levels of these substances (r = 0.62; P < 0.01). This study demonstrates that pentoxifylline treatment was effective in decreasing the levels of TNF-alpha in the serum and PAF levels in the brain of mice infected with the LP-BM5 MuLV.
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PMID:Pentoxifylline decreases brain levels of platelet activating factor in murine AIDS. 915 42


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