UMLS:C0023418 - FACTA Search

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

The effect of thymosin against tumor progression was examined in mice immunosuppressed by cytostatics or X-ray irradiation. When pretreated with cytostatic agents, such as 5-fluorouracil (5-FU) or BCNU, or by X-ray, and then inoculated with P388 or L1210 leukemias, mice died rapidly within a few days. In these systems, thymosin alpha 1 given concomitantly with the cytostatic agents or after X-irradiation prevented rapid death and extended survival, although the mice eventually died with leukemia like normal mice inoculated with cells of the same tumor. Rapid death in the 5-FU-treated mice was also prevented by adoptive transfer of spleen cells from the donor mice if these had been treated with 5-FU plus thymosin alpha 1, but not if they had received 5-FU alone. However, the restorative activity of the donor spleen cells was abrogated by treatment with anti-asialo GM1, but not by treatment with anti-Thy 1 or anti-mouse Ig serum, suggesting that the effector cells in the spleen are NK cells. In fact, thymosin alpha 1, when given concomitantly with 5-FU or after X-irradiation, maintained the NK activity of spleen, which was damaged by treatment with 5-FU or X-irradiation alone. The present study indicates that thymosin alpha 1 exerts a preventive activity against progression of leukemias at least in part through an effect on NK cells or their progenitor cells.
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PMID:Thymosin alpha 1 restores NK-cell activity and prevents tumor progression in mice immunosuppressed by cytostatics or X-rays. 655 15

Mouse thymocytes and spleen cells from unprimed C57BL/6 donors generate broadly reactive cytotoxic cells during 5 days of culture in vitro with polyinosinic acid (5') (poly(I] and/or supernatant from PMA-treated EL4 leukemia cells which contains interleukin 2 (IL-2) activity. We refer here to such cytotoxic cells as "supplement-induced cytotoxic cells" or SICC. Thymocytes are dependent on the supernatant factor(s), whereas spleen cells are usually stimulated by poly(I) alone. Polyinosinic acid acts synergistically with supernatant factor(s) to stimulate generation of SICC by both thymocytes (SICC-T) and spleen cells (SICC-S) when the IL-2 activity of the supernatant is inadequate alone. SICC can be generated by both splenocytes and thymocytes in medium supplemented with fetal calf serum or syngeneic plasma. SICC are active in 4 hr 51Cr-release tests against syngeneic, allogeneic, and xenogeneic tumors but not against lipopolysaccharide-induced lymphoblasts. Embryonic fibroblasts, too, are sensitive to SICC generated by thymocytes. In complement-dependent depletion tests, cytotoxic activity is partially sensitive (SICC-T) or fully sensitive (SICC-S) to anti-Thy-1 and -H-2 but not to anti-Lyt-1, -Lyt-2, or -asialo GM1.
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PMID:Supplement-induced cytotoxic cells (SICC) generated from mouse thymus or spleen cells cultured in the presence of interleukin 2 and/or polyinosinic acid. 660 5

Changes in sialoglycoconjugates and glycosphingolipid (GSL)5 metabolism were demonstrated in mouse EL4, P52 and YAC-1 lymphoma and L1210 leukemia cell lines treated with beta-interferon (IFN). Expression of cell surface (neuraminidase-releasable) sialic acid on IFN-treated cells was markedly elevated (three- to six-fold). The increase in neuraminidase-releasable sialic acid is contributed by sialoglycoproteins and particularly by cell-surface gangliosides in IFN-treated cells. Incorporation of [3H]-galactose into all GSL was elevated in IFN-treated cells. Thin-layer chromatographic analysis of GSL of IFN-treated cells showed an increase in several GSL homologues with striking changes in ganglioside with chromatographic migration of GM2, GM1, and GD1a relative to control cells. IFN-treated tumor-cell lines became resistant to lysis by virus-induced IFN-activated natural killer (NK) cells, as shown previously, but addition of neuraminidase to IFN-treated and untreated cells caused only a moderate increase in NK-sensitivity. This suggests that IFN-mediated protection of target cells from NK lysis was not due to a preferential masking of target structure by elevated levels of sialic acid. These membrane-associated changes in GSL and sialic acid in IFN-treated cells may be potentially significant, because a correlation between certain GSL expression, sialic acid phenotype and susceptibility of target cells to NK-cell-mediated lysis have been found in several other systems.
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PMID:Interferon-induced increase in neuraminidase-releasable sialic acid and glycosphingolipid metabolism in mouse lymphoma and L1210 leukemic cell lines: correlation with susceptibility to natural killer cell-mediated lysis. 683 56

Glycosphingolipids of neutrophils, lymphocytes and leukocytes from patients with various types of human leukemia [acute lymphoblastic (ALL), acute unclassified type (AUL), acute myeloblastic (AML), acute monocytic (AMoL), chronic myeloblastic (CML)] and the hypereosinophilic syndrome (HES) were analyzed chemically and immunochemically. No distinct difference was found in the molar ratio of lipid-bound sialic acid to lipid-bound phosphorus in these cells, but a low ratio of cholesterol to lipid-bound phosphorus was found in ALL (3 of 4 cases), AML, CML and AMoL (one of 2 cases). The predominant glycosphingolipid was ceramide dihexoside (CDH) in all cells analyzed, but the amount and the molar ratio of lipid-bound phosphorus to CDH were clearly different in different cell types, indicating that the molar ratio is a useful criterion in the classification of types of leukemia. In addition, molecular diversity of minor glycosphingolipid components was observed in various leukemic cells. Two of the neutral glycosphingolipids in AMoL were tentatively identified as asialo GM1 and Forssman glycolipids by comparing their mobilities on thin-layer chromatography with those of standard glycolipids and by observing the formation of precipitin lines on a double diffusion agar plate with anti-asialo GM1 and anti-Forssman antibodies.
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PMID:Characterization of glycosphingolipids from cells of various types of human leukemia: occurrence of two glycosphingolipids, one reacting with anti-asialo GM1 antibody and one with anti-Forssman antibody. 688 97

Sialoglycoconjugates and glycosphingolipids were quantitated in a series of variants derived from the YAC-1 lymphoma, known to be highly sensitive to natural killer (NK)-cell-mediated lysis. The variants, which had widely diverging sensitivities to NK cells, were obtained by a number of methods, including selection in the presence of NK cells, antibody to H-2, or antibody to the murine leukemia-virus-induced antigen, and by fusion of sensitive cells with an NK-resistant cell line, A9HT. The sensitivities of these cells to NK-cell-mediated lysis did not correlate with their sensitivities to anti-H-2a cytotoxic T cells. While no correlation could be made between the NK-sensitivity of these variants and their total cellular sialic acid, a statistically significant inverse correlation was observed between the levels of percentage neuraminidase releasable surface sialic acid of total labelled sialyl components and sensitivity to NK cells. This correlation with cell surface sialic acid was observed with either endogenous or lymphocytic choriomeningitis virus-induced activated NK cells as effectors. Neuraminidase treatment of insensitive target cells caused a moderate increase in sensitivity but failed to render the resistant targets as sensitive as YAC-1. Analysis of glycosphingolipids among the variants revealed a strong positive correlation between the total cell neutral glycolipid with chromatographic migration of asialo-GM2 and sensitivity to endogenous or activated NK-cell-mediated lysis. Significant correlations were not found with any other neutral glycolipids. However, ganglioside homologues with chromatographic mobility of GM1, GD1a, GD1b, And GT also showed a positive correlation with both endogenous and activated NK-cell-mediated lysis. The ratio of asialo-GM2 to GM2 had a highly significant positive correlation with sensitivity. These correlative results suggest that asialo-GM2 and certain gangliosides could be involved in binding or lytic events in NK cell:target cell interactions, and that high levels of sialic acid and sialylation on the surface may inhibit and/or modify such interactions. Further studies with these YAC variants should be useful for examining the biochemical bases of target cell-effector cell interactions in the NK-system.
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PMID:Correlation of glycosphingolipids and sialic acid in YAC-1 lymphoma variants with their sensitivity to natural killer-cell-mediated lysis. 730 93

Human T-cell leukemia virus (HTLV) is the etiologic agent of adult T-cell leukemia (ATL), a malignancy of T lymphocytes that is characterized by a long latency period after virus exposure. Intraperitoneal inoculation of severe combined immunodeficient (SCID) mice with HTLV-transformed cell lines and ATL tumor cells was employed to investigate the tumorigenic potential of HTLV type I (HTLV-I)-infected cells. In contrast to inoculation of ATL (RV-ATL) cells into SCID mice, which resulted in the formation of lymphomas, inoculation of HTLV-I- and HTLV-II-transformed cell lines (SLB-I and JLB-II cells, respectively) did not result in tumor formation. Immunosuppression of SCID mice, either by whole-body irradiation or by treatment with an antiserum, anti-asialo GM1 (alpha-AGM1), which transiently abrogates natural killer cell activity in vivo, was necessary to establish the growth of tumors derived from HTLV-transformed cell lines. PCR and flow cytometric studies reveal that HTLV-I-transformed cells are eliminated from the peritoneal cavities of inoculated mice by 3 days postinoculation; in contrast, RV-ATL cells persist and are detected until the mice succumb to lymphoma development. The differing behaviors of HTLV-infected cell lines and ATL tumor cells in SCID mice suggest that ATL cells have a higher tumorigenic potential in vivo than do HTLV-infected cell lines because of their ability to evade natural killer cell-mediated cytolysis.
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PMID:Potential role of natural killer cells in controlling tumorigenesis by human T-cell leukemia viruses. 781 16

Studies were performed to examine whether, in addition to T cells, there might be other immune cells also capable of exerting a graft-versus-leukemia (GVL) response following allogeneic marrow transplant. Using an MHC-matched mouse model, consisting of normal B10.S donors and SJL/J Rauscher-retroviral-leukemic recipients, the donor cells were selectively depleted of their Asialo-GM1+ component prior to being infused into the leukemic recipients. The incidence of relapse was then compared against that for matched leukemic control recipients of undepleted cells from the same donors. FCM analysis of the depletion protocol indicated that exposure to anti-Asialo-GM1 antibody eliminated more than half of the donor NK1.1+ cells, but caused no significant losses among the Thy-1+, CD3+, or CD8+ cells. Nevertheless, fatal relapse among the leukemic recipients of the depleted cells was nearly double that found among the leukemic control recipients of undepleted cells, 47.5 vs 25.4% (P = 0.01). In a parallel study, using normal SJL/J recipients, this same depletion protocol was found to have no significant effect on the incidence of graft-versus-host disease (GVHD). These results therefore suggest that Asialo-GM1+ NK cells may be capable of contributing to the suppression of relapse in this type of leukemic recipient of allogeneic marrow, and that this suppression may occur independently of GVHD.
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PMID:Evidence for a possible role of Asialo-GM1-positive cells in the graft-versus-leukemia repression of a murine type-C retroviral leukemia. 853 19

The role of various cell subpopulations involved in the graft-versus-leukemia (GVL) effect induced by allogeneic bone marrow transplantation (BMT) was investigated in (BALB/c x C57BL/6)F1 (F1) recipients, inoculated with murine B cell leukemia (BCL1), by using monoclonal murine anti-IL-2 receptor antibodies or rabbit anti-Asialo GM1 antibodies directed predominantly against murine NK cells. F1 mice with BCL1 were irradiated and reconstituted with parental (C57BL/6) bone marrow cells (BMC) or a mixture of BMC and spleen cells and treated in vivo for 10 days with anti-IL-2 receptor antibody or anti-Asialo-GM1 antibody. Both treatments lessened the GVL effects induced by the allograft and resulted in development of leukemia relapse, as documented in vivo by adoptive transfer of 10(5) spleen cells obtained from treated mice into secondary syngeneic adoptive recipients. Our data indicate that IL-2 receptor-positive T cells and possibly IL-2-activated allogeneic NK cells play a key role in inducing GVL following allogeneic BMT.
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PMID:The role of antibodies to IL-2 receptor and Asialo GM1 on graft-versus-leukemia effects induced by bone marrow allografts in murine B cell leukemia. 853 20

The murine leukemia cell lines L1210 and WEHI-3B show a very different sensitivity to the cholera toxin (CT). The in vitro growth of L1210 is completely inhibited by 10(-8) M CT, while WEHI-3B growth shows the same inhibition at 10(-11) M. The analysis of membrane ganglioside pattern of the two cell lines shows that in L1210 cells the major component is the GM1a ganglioside while the monosialogangl oside fraction from WEHI-3B is entirely composed of gangliosides of the 'b' series among which GM1b is the more represented. The total cholera toxin binding capacity of the ganglioside extract from L1210 cells is more than hundred fold higher than that of WEHI-3B and this difference is also confirmed by the number of CT receptors/cell and by the binding of FITC-B subunit of CT on the cells. These surprising data are in conflict with the poor sensitivity to CT evidenced by L1210 compared to WEHI-3B cells. In order to clarify this discrepancy we investigated the cAMP accumulation, the cell viability and the clonogenicity of these two leukemia cell lines following the treatment with CT and forskolin (FRSK). The treatment of WEHI-3B cells with CT induces a dramatic increase of intracellular cAMP which highly correlates with cell death and the decrease of clonogenicity and this result is partially obtained by the treatment with FRSK. L1210 cells do not evidence significant cAMP accumulation neither with CT nor with FRSK treatment. These data suggest that the different inhibiting effect of CT on WEHI-3B and L1210 cells does not correlate with their different pattern of gangliosides and the related toxin binding capacity. Further they indicate that the growth inhibition of WEHI-3B cells is closely related with a cAMP-dependent cell killing mechanism, while the inhibition of L1210 growth (produced by high concentration of CT) is mediated by a cAMP independent mechanism.
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PMID:The different inhibiting effect of cholera toxin on two leukemia cell lines does not correlate with their toxin binding capacity. 875 Nov 56

Met-ase-1 is a 30 000 Mr serine protease (granzyme) that was first isolated in the cytolytic granules of rat CD3(-) large granular lymphocytes. We screened a mouse genomic library with rat Met-ase-1 cDNA, and obtained bacteriophage clones that contained the mouse Met-ase-1 gene. The mouse Met-ase-1 gene comprises five exons spanning approximately 5.2 kilobases (kb) and exhibits a similar structural organization to its rat homologue and a family of neutrophil elastase-like serine proteases. Mouse Met-ase-1 mRNA was only detected in total cellular and poly A mRNA of mouse CD3(-) GM1(+) large granular lymphocytes derived from splenocytes stimulated with IL-2 and the mouse NK1.1(+) cell line 4 - 16. Spleen T-cell populations generated by Concanavalin A stimulation and a number of mouse pre-NK and T cell lines did not express mouse Met-ase-1 mRNA. The 5' flanking region of the mouse Met-ase-1 gene also shares considerable regions of identity with the 5' flanking region of the rat Met-ase-1 gene. A 3.3 kb segment of 5' sequence flanking the mouse Met-ase-1 gene was inserted upstream of the chloramphenicol acetyltransferase reporter gene and this construct transiently transfected into a variety of mouse and rat large granular lymphocyte leukemia and T-cell lines. The transcriptional activity of the mouse Met-ase-1 5' flanking region was significant in the RNK-16 large granular lymphocyte leukemia, strongest in the 4 - 16 mouse NK1.1(+) cell line, and weak in several mouse pre-NK cell lines. Reverse transcriptase polymerase chain reaction of mouse large granular lymphocyte mRNA was used to derive the full-length coding sequence for mouse Met-ase-1. The predicted hexapropeptide of mouse Met-ase-1 (Asn-6 to Gln-1), was deleted by polymerase chain reaction mutagenesis to enable expression of active mouse Met-ase-1 in mammalian COS-7 cells. Northern blot analysis and protease assays of transfected COS cell lysates against a panel of thiobenzyl ester substrates formally demonstrated that the mouse Met-ase-1 gene encodes a serine proteinase that hydrolyzes substrates containing a long narrow hydrophobic amino acids like methionine, norleucine, and leucine in the P1.
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PMID:Cloning and expression of the recombinant mouse natural killer cell granzyme Met-ase-1. 878 Nov 19

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