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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The extreme host specificity of pathogenic neisseriae limits investigations aimed at the analysis of bacterial-host interactions almost completely to the use of in vitro models. Although permanent epithelial and endothelial cell lines are already indispensable tools with respect to initial infection processes, studies concerning the interaction of neisseriae with phagocytic cells have been confined to primary human blood cells. We investigated the use of human leukemia-derived monocytic and myelomonocytic cell lines that can be differentiated in vitro towards phagocytic cells by a panel of chemical and biological reagents including cytokines, vitamin analogs, and antileukemia drugs. Whereas tumor necrosis factor alpha, gamma interferon, bufalin, or granulocyte-macrophage colony-stimulating factor only marginally increased the ability of monocytic MonoMac-6 and myelomonocytic JOSK-M cells to interact with the bacteria, retinoic acid and vitamin D3 treatment for 2 to 4 days led to highly phagocytic cells that internalized gonococci in an Opa protein-specific manner. This is comparable to the phagocytosis by primary monocytes from human blood, where more than 80% of cells are infected with intracellular bacteria. The increased phagocytic activity of JOSK-M cells following in vitro differentiation was paralleled by enhanced oxidative burst capacity. Whereas undifferentiated cells responded to neither phorbol 12-myristate 13-acetate nor other known soluble and particulate stimuli, cells incubated with retinoic acid and bufalin showed the same pattern and the same intensity of oxidative burst activity in response to Neisseria gonorrhoeae as primary cells: Opa-expressing gonococci elicited an oxidative burst, whereas Opa- gonococci did not. The surface expression of major histocompatibility complex (MHC) class II molecules was only slightly changed after retinoic acid treatment. Also, phagocytosis of gonococci had no influence on MHC class II surface expression. Taken together, our results demonstrate that in vitro-differentiated human myelomonocytic JOSK-M cells provide a suitable model for the study of a variety of aspects of the gonococcal interaction with phagocytes.
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PMID:An in vitro-differentiated human cell line as a model system to study the interaction of Neisseria gonorrhoeae with phagocytic cells. 912 73

Triggering of HLA class II antigens by the anti-HLA-DR monoclonal antibody (mAb) L243 significantly (P < 0.05) and differentially enhanced the release of tumor necrosis factor alpha (TNF-alpha) by the non-Hodgkin's lymphoma cells Ri-I, Ci-I, and Sc-I, which are at a distinct stage of B-cell differentiation, and by the more mature Burkitt lymphoma cell Raji; in contrast, it did not induce TNF-alpha release by the pre-B leukemia cells Nalm-6 and BV173. TNF-alpha release peaked at 24 h and decreased thereafter, and it was dose dependent and preceded by an increase of TNF-alpha mRNA detectable after 3 h of stimulation with mAb L243. Secreted TNF-alpha mediated the enhancement of nuclear factor kappa B (NF-kappa B) and activator protein-1 (AP-1) binding activity; in fact, the triggering of HLA-DR antigens in the presence of antihuman TNF-alpha-neutralizing antibodies did not upregulate NF-kappa B and AP-1. In contrast, released TNF-alpha was not responsible for the homotypic aggregation of Ri-I, Ci-I, Sc-I, and Raji cells induced by mAb L243, and it did not affect the proliferation of B cells investigated. Altogether, our data demonstrate that: (a) the ability of B cells to release TNF-alpha after triggering of HLA-DR antigens depends on their stage of differentiation; (b) levels of released TNF-alpha seem to correlate with the stage of B-cell maturation but do not correlate with the amounts of cell surface HLA-DR antigens; (c) secreted TNF-alpha regulates the levels of expression of NF-kappa B and AP-1 by an autocrine loop; and (d) intracellular signals mediating TNF-alpha release by B cells are distinct from those regulating homotypic aggregation and proliferation.
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PMID:Triggering of HLA-DR antigens differentially modulates tumor necrosis factor alpha release by B cells at distinct stage of maturation. 914 9

Based on previously published observations regarding the protective effects of interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha) against gamma radiation, alkylating agents and ultraviolet radiation, we hypothesized that the protection against such DNA damaging treatments can be the result of a 'stress'-like response induced by these cytokines and mediated by early response cellular gene(s). By applying the mRNA differential display to RNA obtained from A549 lung carcinoma cell line that was incubated with 50 ng/ml IL-1 for 0, 1, 2, and 6 h, we identified several cDNA fragments that correspond to genes regulated by IL-1. The full length cDNA for one fragment was obtained using 5'RACE, cloned, sequenced, and found to be homologous to human A1, a Bcl-2-related gene. In this study, we report that the expression of human A1 is either absent or present at low levels in leukemic cells, while it is expressed in human bone marrow cells and abundant in peripheral blood progenitors. It is induced by IL-1 and TNF alpha in A549 lung carcinoma, bone marrow, and certain leukemic cells. A1 is also induced in leukemic cells during granulocytic or macrophage but not erythroid differentiation. In conclusion, this is the first demonstration that A1 is inducible by cytokines in human bone marrow and certain tumor cells as well as myeloid differentiation in leukemic cells.
Leukemia 1997 Jul
PMID:Human A1, a Bcl-2-related gene, is induced in leukemic cells by cytokines as well as differentiating factors. 920 81

In 93 newly diagnosed lymphoma patients, tumor necrosis factor alpha (TNF alpha) and its p55 soluble receptor (p55-sR), were prospectively determined in plasma by IRMA and ELISA methods respectively. These 93 patients included 31 patients with low grade lymphoma, 55 with intermediate or high grade lymphoma and 7 with Hodgkin's disease. Median TNF alpha plasma values were 20 pg/mL (range 5-380 pg/mL) in patients versus 7 pg/mL (range 4-9 pg/mL) in healthy control subjects. Presence of TNF alpha level equal or greater than 20 pg/mL was significantly associated with elevated LDH level, serum beta 2-microglobulin level > or = 3 mg/L, hemoglobin < or = 12 g/dL, Ann Arbor stage III or IV disease, and with bulky tumor. High level of TNF alpha was also associated, although less strongly, with B symptoms, poor performance status, and serum albumin < or = 35 g/L, yet it was not associated with change in acute phase protein levels. Levels of p55-sR were also markedly elevated in these lymphoma patients (median of 3.5 ng/mL, range 0.8-18.8 ng/mL) versus 1.45 ng/mL in control subjects (range 1.1-2.3 ng/mL). Level of p55-sR equal or greater than 3.5 ng/mL was significantly associated with poor performance status, B symptoms, beta 2-microglobulin levels > or = 3 mg/L, serum albumin < or = 35 g/L, C-reactive protein > 6 mg/L, hemoglobin < or = 12 g/dL, and bulky tumor. In the whole group of 93 patients, both high TNF alpha and p55-sR levels strongly predicted short freedom from progression and overall survival. This study suggests that elevated TNF alpha and p55-sR plasma levels have a high correlation with other adverse prognostic factors in lymphoma patients and predict their poor outcome.
Leukemia 1997 Apr
PMID:Prognostic significance of TNF alpha and its p55 soluble receptor in malignant lymphomas. 920 18

Differentiation-inducing factor-1 (DIF-1) is a putative morphogen that induces stalk cell formation in the cellular slime mold Dictyostelium discoideum. In this study, we have examined the effects of DIF-1 on the human leukemia HL-60 cells. DIF-1 at 10-40 microM suppressed cell growth in a dose-dependent manner, and approximately 50% growth inhibition was attained with 15-20 microM DIF-1. FACS analysis of cell-cycle phase distribution using propidium iodide revealed that many cells were accumulated in the G1 phase after treatment with 15-20 microM DIF-1. These concentrations of DIF-1 also raised [Ca2+]i in a dose-dependent manner irrespective of the presence of extracellular Ca2+, indicating that DIF-1 elicited Ca2+-release from some intracellular Ca2+ store(s). Most importantly, relatively low concentrations of DIF-1 (1-5 microM) were found to promote retinoic acid-induced cell differentiation. The present results indicate that DIF-1 may be a useful tool for the analysis of myeloid cell differentiation and have therapeutic potential in the treatment of human myeloid leukemia.
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PMID:DIF-1, putative morphogen of D. discoideum, suppresses cell growth and promotes retinoic acid-induced cell differentiation in HL-60. 924 Apr 52

Hexadecylphosphocholine (HePC) is the main representative of a new group of antineoplastic agents, the alkylphosphocholines, which were originally derived from cytotoxic etherlysophospholipids. HePC shows antiproliferative action against a whole variety of tumor cells and tumors in vitro and in vivo. Furthermore, it also induces differentiation in some hematologic cell lines and prevents invasive growth of neoplastic cells in vitro. To date, the precise molecular mechanisms mediating the biological effects of HePC have not been identified yet. As etherlysophospholipids seem to inhibit some pathways of lipid-dependent intracellular signalling, similar effects may be relevant for HePC. We therefore investigated the influence of HePC on phospholipase A2 (PLA2-EC 3.1.1) in the human leukemia cell line U 937. HePC seems to inhibit enzyme activity independently of protein kinase C (PKC) in differentiated U 937 cells stimulated by tumor necrosis factor alpha (TNFalpha). Inhibition of purified secretory PLA2 from snake venom (EC 3.1.1.4) in vitro shows characteristics of a non-competitive mode. In contrast, HePC leads to an enhancement of PLA2 activity in immature cells which cannot be explained by changes in membrane composition. Our data suggest that PLA, inhibition is most probably not the mechanism by which HePC mediates its antiproliferative effects.
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PMID:Differential regulation of phospholipase A2 in human leukemia cells by the etherphospholipid analogue hexadecylphosphocholine. 926 26

Granulocyte-macrophage colony-stimulating factor (GM-CSF ) and tumor necrosis factor alpha (TNFalpha) have been implicated in the pathogenesis of the fatal childhood disease termed juvenile myelomonocytic leukemia (JMML). We used a severe combined immunodeficient/nonobese diabetic (SCID/NOD) mouse model of JMML and examined the effect of inhibiting these cytokines in vivo with the human GM-CSF antagonist and apoptotic agent E21R and the anti-TNFalpha monoclonal antibody (MoAb) cA2 on JMML cell growth and dissemination in vivo. We show here that JMML cells repopulated to high levels in the absence of exogeneous growth factors. Administration of E21R at the time of transplantation or 4 weeks after profoundly reduced JMML cell load in the mouse bone marrow. In contrast, MoAb cA2 had no effect on its own, but synergized with E21R in virtually eliminating JMML cells from the mouse bone marrow. In the spleen and peripheral blood, E21R eliminated JMML cells, while MoAb cA2 had no effect. Importantly, studies of mice engrafted simultaneously with cells from both normal donors and from JMML patients showed that E21R preferentially eliminated leukemic cells. This is the first time a specific GM-CSF inhibitor has been used in vivo, and the results suggest that GM-CSF plays a major role in the pathogenesis of JMML. E21R might offer a novel and specific approach for the treatment of this aggressive leukemia in man.
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PMID:Inhibition of granulocyte-macrophage colony-stimulating factor prevents dissemination and induces remission of juvenile myelomonocytic leukemia in engrafted immunodeficient mice. 938 8

Infection of neonatal mice with ts1, the neuropathogenic mutant of the Moloney murine leukemia virus, results in motor neuronal death in the brainstem and the spinal cord, with gliosis and demyelination, but no inflammatory cell infiltration into the CNS. To evaluate the possible mechanism(s) of ts1-induced neuropathogenesis, we measured CNS expression of cytokines and cell death-related genes in ts1-infected mice with neurological signs and compared with control uninfected mice. In the brainstem, the expression of Fas and tumor necrosis factor alpha (TNF-alpha) was increased in the ts1-infected mice. Both TNF-alpha and Fas were detected in astrocytes, and Fas was also detected in neurons in the brainstem. Some TNF-alpha-immunolabeled cells also appeared to be microglial cells. Most Fas-positive cells, including astrocytes and neurons, showed cytoplasmic vacuolization and other degenerative changes. In addition, Fas ligand-immunolabeled cells were also detected in sites where spongiform degeneration occurred. This study suggests that neural cell death in ts1-induced neurodegeneration is likely due to Fas- and TNF-alpha-mediated cell death mechanisms.
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PMID:Neurodegeneration induced by MoMuLV-ts1 and increased expression of Fas and TNF-alpha in the central nervous system. 947 60

Human malignant cells are targeted by homologous complement C3b if they express M161Ag, a 43-kDa protein with C3-activating property. cDNA of M161Ag cloned from human leukemia cell lines predicted M161Ag as a novel secretory protein comprised of 428 amino acids including 5 amino acids encoded by TGA codons (Matsumoto M., Takeda, J., Inoue, N., Hara, T., Hatanaka, M., Takahashi, K., Nagasawa, S., Akedo, H., and Seya, T. (1997) Nat. Med. 3, 1266-1270), although the origin of this gene was obscure. Here we clarified this point through genomic and biochemical analysis: 1) 5'-UT and genomic sequences represented the prokaryote promoter and ribosomal binding site; 2) the TGA codons in M161Ag cDNA were translated not into selenocysteines but into tryptophans; 3) M161Ag anchored onto the membrane secondary to its N-terminal palmitoylation like prokaryote lipoproteins; 4) genomic and cDNA clones of M161Ag were highly homologous to Mycoplasma fermentans gene encoding P48, a monocytic differentiation/activation factor, recently released in the data base, although the resultant proteins were different in the amino acid sequences. Additionally, purified soluble M161Ag efficiently provoked IL-1beta, tumor necrosis factor alpha, and IL-6 like P48, and further IL-10 and IL-12 in human peripheral blood monocytes. Thus, M161Ag originates from M. fermentans, and latently infected M. fermentans allows human cells to produce M161Ag. The liberated protein serves as a potent modulator of innate and cellular immune responses via its complement-activating and cytokine-producing activities.
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PMID:Structural and functional properties of complement-activating protein M161Ag, a Mycoplasma fermentans gene product that induces cytokine production by human monocytes. 957 96

The interactions of 2',2'-difluorodeoxycytidine (gemcitabine) with tumor necrosis factor alpha (TNF-alpha) or its mutein VI on the survival time of mice bearing L1210 and P388 leukemia was investigated. Four hundred eighty male CD2F1 mice were used in the experiments. They were given gemcitabine (20 mg/kg) on days 1, 4, 7 and 10 after i.p. inoculation with leukemic cells (day 0). Cytokines were administered i.p. at a dose of 250 microg/kg as daily injections for 8 days or at a dose of 400 microg/kg given 2, 4, 6 and 8 days after day 0. Drugs were administered alone and in combination. Our study indicates that TNF-alpha and its mutein VI decrease the antileukemic effect of gemcitabine on murine leukemias L1210 and P388.
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PMID:Interactions of 2',2'-diflurodeoxycytidine (gemcitabine) with tumor necrosis factor alpha or its mutein VI in murine leukemias L1210 and P388. 961 9


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