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

A number of cloned biologic factors are currently available that are candidates for therapy of myelodysplastic syndromes and, by extension, acute nonlymphoblastic leukemia. gamma-Interferon and, to a greater extent, tumor necrosis factor exhibit leukemic differentiative effects without the potential for stimulation of leukemic clones. These effects may be enhanced by combinations of these with one another or with chemical inducers of differentiation such as retinoic acid or vitamin D derivatives. The colony-stimulating factors clearly have potent in vivo effects upon hematopoiesis. The lineage specific factors (G- or M-CSF) may have greater differentiation induction potential and less risk of accelerating emergence of leukemic clones than the earlier acting factors (GM- or multi-CSF). Thus, several potentially fruitful avenues for clinical research are currently available.
Leukemia 1988 Jun
PMID:The basis for treatment of myelodysplastic syndrome and acute nonlymphoblastic leukemia with biologic agents. 245 61

Recent progress in biotechnology has uncovered the presence of trace substances which participate in the immunological response between cancer and host; They are cytokines, monoclonal antibodies, and immunomodulating agents produced by effector cells which are called macrophage, NK cells and lymphocytes of cancer patients. Recent genetic engineering enables mass production of these substances, and their clinical application in treating human cancers is expected to take place in the near future. In this paper, the recent trend of cancer treatment, using various cytokines are briefly introduced, namely interferon, interleukin-2, tumor necrosis factor and colony stimulating factor. Although IL-2 is effective for the activation of T-lymphocyte, intravenous injection of IL-2 is not so effective for treatment of cancer-patients. On the other hand, IL-2-activated killer cells (LAK cells) are potent effectors of adoptive immunotherapy in advanced cancer patients. The clinical study was conducted in 25 patients with advanced carcinomas. Therapeutic efficacy was obtained in patients for whom local transfer was undertaken rather than systemic administration. Tumor necrosis factor, a cytotoxin derived from macrophages shows much promise for application in cancer therapy because of its marked antitumor effects and its high specificity to tumors. Clinical study was performed on leukemia patients who showed marked decreases of percentage of leukemic cells in peripheral blood. Moreover, local injection of TNF was very effective for the decrease of tumor size in patients with hepatoma and subcutaneous tumor. In addition, to clinical results using CSF and interferon are reported.
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PMID:[Recent trends in cancer treatment using cytokines]. 247 55

A growth-inhibitory (GI) factor, that specifically inhibits the growth of mouse monocytic leukemia cells, was found in conditioned medium of mouse lung tissue, but not in that of mouse brain, heart, liver, or kidney tissue. Conditioned medium of spleen or bone marrow cells had low GI activity. Pulmonary macrophages were as active as peritoneal and bone-marrow-derived macrophages in production of the GI activity. The GI factor inhibited the growth of murine monocytic leukemia cell lines Mm-A and J774.1, but scarcely inhibited the growth of other mouse cell lines, such as a myeloblastic leukemia cell line (M1), a Friend erythroleukemia cell line (745A) and a mammary carcinoma cell line (FM3A). It had no significant effect on the growth of human monocytic leukemia cell lines U937 and THP-1 or on the HL-60 promyelocytic leukemia cell line. These results suggest that the GI factor produced by mouse lung tissue preferentially inhibits the growth of mouse monocytic cells. The GI factor was found to be a proteinaceous substance with a molecular mass of 25 kDa. On chromatofocusing, the GI activity was eluted with Polybuffer 96/acetic acid at pH 7.2-7.5. The GI activity was not significantly decreased by heat treatment at 56 degrees C for 30 min or acid treatment (0.01 M HCl, 14 h), but the GI activity in glycosidase-treated conditioned medium of lung tissue was lost on heat treatment. The GI activity could not be neutralized with anti-(interferon alpha + beta) antibody. The activity was produced constitutively by lung tissues and its production was not stimulated appreciably by lipopolysaccharide, lectin, or poly(I).poly(C). The GI factor appears to be a cytokine unrelated to known cytokines such as tumor necrosis factor, interleukin-1, transforming growth factor beta, and interferons. These results suggest that the GI factor may be involved in negative feedback regulation of macrophage production in steady-state conditions in the lungs.
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PMID:Normal mouse lung tissue produces a growth-inhibitory factor(s) preferential for mouse monocytic leukemia cells. 248 Aug 47

Recombinant tumor necrosis factor (rTNF) and rIFN-gamma induce in the human leukemia cell lines HL-60, ML3, and U937 the accumulation of transcripts of the X chromosome-linked chronic granulomatous disease (X-CGD) gene, encoding the 91-kD heavy chain of cytochrome b-245, a component of the NADPH oxidase of phagocytic cells. The gene is induced within 6 h by either cytokine, and its accumulation is observed upon induction with rIFN-gamma up to 5 d. The combined effect of the two cytokines is more than additive. rIFN-gamma also induces accumulation of X-CGD mRNA in immature myeloid cells from peripheral blood of chronic myeloid leukemia (CML) patients, whereas rTNF has almost no effect. The cells from CML patients constitutively express TNF mRNA, suggesting that endogenously produced TNF may play a role in the effect of rIFN-gamma on these cells. rTNF induces X-CGD gene expression in the myeloid cell lines acting, at least in part, at the transcriptional level, as shown in nuclear run-on experiments. The gene encoding the 22-kD light chain of cytochrome b-245 is constitutively expressed in the human myeloid cell lines and the accumulation of its transcripts is affected by neither rTNF nor rIFN-gamma, rTNF and rIFN-gamma synergistically to induce the cell lines to express the cytochrome b-245 heterodimer (as evaluated by its visible spectrum), and to produce NADPH oxidase activity and H2O2 upon stimulation with phorbol diesters.
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PMID:Tumor necrosis factor and immune interferon synergistically induce cytochrome b-245 heavy-chain gene expression and nicotinamide-adenine dinucleotide phosphate hydrogenase oxidase in human leukemic myeloid cells. 249 43

alpha-N-(3-Acyloxyacyl)-ornithine (or -serine) is the structure of lipoamino acids obtained by us previously from some gram-negative bacteria (Y. Kawai and I. Yano, Eur. J. Biochem. 136:531-538, 1983; Y. Kawai, I. Yano, and K. Kaneda, Eur. J. Biochem. 171:73-80, 1988; Y. Kawai, I. Yano, K. Kaneda, and E. Yabuuchi, Eur. J. Biochem. 175:633-641, 1988). The 3-acyloxyacylamide structure is present in both the lipoamino acids and lipid A of lipopolysaccharide (endotoxin). The efficacy of lipoamino acids (an ornithine-containing lipid and a serine-containing lipid) in activating C3H/HeSlc mouse peritoneal exudate macrophages was compared with that of bacterial lipopolysaccharide, because the two types of substances were expected to exhibit similar biological activities and physiological functions on the basis of their structural similarities. Actually, the lipoamino acids, as well as lipopolysaccharide, strongly activated the macrophages to generate the immunoregulatory substances prostaglandin E2 and interleukin-1, but their effect on the induction of L929 cell cytolytic factor (a possible tumor necrosis factor), another immunoregulatory substance, was weaker than that of lipopolysaccharide. The effect of lipoamino acids on the cytotoxicity of macrophages for EL-4 leukemia cells was very weak. However, all of these activities, as far as tested, were strongly enhanced by synergistic action with gamma interferon. Only the serine-containing lipid killed both C3H/HeSlc and C3H/HeJ macrophages to almost the same degree as endotoxin killed C3H/HeSlc macrophages. On the other hand, lethal toxicity for mice was not found with either the ornithine-containing lipid or the serine-containing lipid, even when 7 mg of compound was injected into a mouse. These studies suggest that the lipoamino acids are nontoxic characteristic immunoactivators.
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PMID:Macrophage activation by an ornithine-containing lipid or a serine-containing lipid. 249 44

Recombinant tumor necrosis factor and/or gamma-interferon were injected into C57BL/Ka mice after completion of a whole body split dose irradiation, which usually induces thymic lymphomas in more than 90% of the animals. The survival and the incidence of thymic lymphomas were significantly reduced in the cytokine-injected irradiated mice. The protective effect was similar to that obtained by grafting normal bone marrow cells after irradiation. The mechanisms of lymphoma inhibition by TNF or IFN-gamma are discussed.
Leukemia 1989 Aug
PMID:Tumor necrosis factor and interferon gamma inhibit the development of radiation-induced thymic lymphomas in C57BL/Ka mice. 250 94

The effects of the tumor necrosis factor (TNF), and a second pleiotropic cytokine interferon-gamma (IFN), were examined in a line of human myeloblastic leukemia cells (ML-1). By itself, TNF causes ML-1 to differentiate along the monocytic pathway. The cells exhibit an increase in Fc receptors and acquire the morphological characteristics of maturing phenotype. They remain viable and continue to proliferate (at greater than or equal to 50% of the control growth rate) even with 10(2)-10(4) units/ml TNF. IFN alone has similar effects, causing an increase in Fc receptors but little cytotoxicity. In contrast to either cytokine alone, the combination of TNF plus IFN causes a cessation of proliferation and extensive cell death. Cytotoxicity occurs in a synergistic fashion; it requires the simultaneous presence of both cytokines, occurring with concurrent but not sequential exposure. These different responses, differentiation (TNF alone) and cytotoxicity (TNF + IFN), occur with a similar range of doses (approximately 10(2)-10(4) units/ml) and in a similar time frame (beginning on day 2). In other cell types, IFN can augment either the differentiation-inducing or the cytotoxic effect of TNF. In ML-1, the combined application of TNF plus IFN results in a shift from differentiation to cytotoxicity.
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PMID:Differentiation-inducing and cytotoxic effects of tumor necrosis factor and interferon-gamma in myeloblastic ML-1 cells. 250 96

2',3'-dideoxycytidine (ddC) inhibits replication of the immunodeficiency inducing strain of feline leukemia virus (FeLV-FAIDS) in vitro at concentrations ranging from 1-10 micrograms/ml. Additive antiviral effect is achieved when ddC is combined with either human recombinant alpha interferon (IFN alpha) or tumor necrosis factor (TNF) plus IFN alpha. Initial in vivo pharmacokinetic studies in cats, utilizing bolus intravenous administration of ddC (20 mg/kg), resulted in peak plasma concentrations of 15 micrograms/ml 1 min after administration and a half-life of approximately 1 h. These values could not be augmented with high levels of the deaminase blocker tetrahydrouridine administered prior to or concurrently with ddC. In vivo trials utilizing multiple, daily intravenous injections of ddC could not prevent the development of persistent viremia in cats infected with FeLV-FAIDS. To enhance ddC pharmacokinetics and antiviral activity, controlled release capsular implants were developed by blending ddC with a copolymer consisting of DL-lactide glycolide and hydroxypropyl cellulose, which was melt-spun into fibers and encapsulated in a sheath of polyethylene glycol for subcutaneous implantation. Pharmacokinetic studies, conducted in cats receiving an average dose of 600 mg of ddC, indicated an average peak plasma concentration of 17 micrograms/ml achieved at 6 h post implantation with 3.5 micrograms/ml noted at 48 h; and an extension of plasma half-life from 1.5 (bolus subcutaneous injection) to 20 h. sustained plasma concentrations of 1.5 to 10 micrograms/ml, equivalent to ddC levels previously shown to have anti-FeLV activity in vitro, were maintained throughout a 72 h period. Implantation devices could be replenished every 48 h and elevated plasma levels were sustained for four weeks without signs of clinical toxicity, sepsis or significant alterations in the hemogram. Initial clinical trials employing controlled release capsular ddC implants in vivo indicate significant retardation of FeLV-FAIDS replication throughout a four week treatment period.
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PMID:Treatment of FeLV-induced immunodeficiency syndrome (FeLV-FAIDS) with controlled release capsular implantation of 2',3'-dideoxycytidine. 254 37

An immunoglobulin M (IgM)-positive cell line, Ms 28, apparently spontaneously transformed by Epstein-Barr virus (EBV) was established from peripheral blood cells of a patient with immature myeloblastic leukemia. It has been characterized according to phenotype, cytochemistry, and membrane antigen pattern. The cell line expresses lymphoid markers like CD 19, CD 22, and CD 30 and synthesizes and secretes IgM. Monocyte markers CD 11c, CD 14, and CD 15 are absent. Neither interleukin-1 (IL-1), nor tumor necrosis factor (TNF-alpha) are produced. But Ms 28 cells show strong phagocytic activity and engulf Latex particles and sheep RBCs (SRBCs) that need not to be opsonized. The phagocytic activity can be inhibited by chloroquine. Both phagocytosis and EBV nuclear-antigen (EBNA) expression can be observed in one and the same cell. Ms 28 cells might be useful to study immunologic activities like antigen processing and presentation.
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PMID:Establishment and characterization of an Epstein-Barr virus transformed cell line with strong phagocytic activity. 254 24

Cell lysates of the human monoblastic leukemia cell line, THP-1, have procoagulant activity (PCA) that is Ca++-dependent and not demonstrable in either Factor VII-, or Factor X-deficient plasma. The PCA of THP-1 cells was enhanced by human recombinant tumor necrosis factor-alpha (TNF-alpha) up to five fold. There was a dose-dependent increase in PCA when THP-1 cells were cultured with concentrations of TNF-alpha, up to 10 U/ml. PCA of cell lysates or whole cell preparations was measured in comparison to a rabbit brain thromboplastin standard. The effect of TNF-alpha was enhanced by recombinant human interferon-gamma (IFN-gamma). Cycloheximide inhibited the induction of PCA by THP-1 cells, which shows that the protein synthesis is essential to mediate the effect of TNF-alpha. THP-1 cells and U937 cells bound 125I-labeled TNF specifically. The numbers of receptors per cell were found to be 1,890 and 1,550 for THP-1 and U937 cells, respectively. Other lymphoid and myeloblastic leukemia cell lines examined did not have TNF receptors, indicating that the effect of TNF-alpha is mediated by the receptors on the cell surface.
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PMID:Induction of tissue factor-like activity of human monoblastic leukemia cell line by tumor necrosis factor-alpha. 255 90


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