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 binding of urokinase-type plasminogen activator (u-PA) to its receptor (u-PA-R) is required for morphological and functional maturation during monocyte differentiation of the promyelocytic leukaemia line HL-60. This paper reports that monocyte differentiation of HL-60 cells induced by 1,25 dihydroxyvitamin D2 (vitamin D2) results in a marked increase in expression of u-PA and u-PA-R. This increase in u-PA expression is of greater magnitude than is observed after culture with interferon-gamma (IFN gamma), another potent inducer of monocytic differentiation. Dimethyl sulphoxide (DMSO), an agent that induces granulocytic differentiation, also increased expression of u-PA. However, culture with the granulocyte-inducing all-trans retinoic acid (RA) did not induce an increase in surface expression of u-PA or u-PA-R. The vitamin D2-induced increase in cell-surface u-PA was not coincident with an increase in steady-state levels of u-PA mRNA, suggesting that intracellular stores of this protein, translational or post-translational mechanisms of regulation, or some other regulatory mechanism may be responsible for the increase in u-PA during differentiation. To ascertain an association between the increased expression of cell-surface u-PA and reduced proliferation that accompanies differentiation, the effect of u-PA on cellular proliferation of HL-60 cells was measured. Both pro-u-PA (whole molecule) and fragments of u-PA that retained receptor-binding capability caused a marked inhibition of HL-60 proliferation in the absence of vitamin D2.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Urokinase inhibits HL-60 cell proliferation in vitro. 784 Dec 98

The anthracycline antitumor antibiotic aclarubicin is known to induce granulocytic differentiation in the human myeloid leukemia cell line HL-60. We investigated whether this effect is accompanied by changes in the expression of the protooncogenes c-myc and c-myb. Treatment of HL-60 cells with aclarubicin, 50 nM, caused a rapid decrease in c-myc and c-myb mRNA levels within 1 h and 2 h, respectively. In parallel, we demonstrated a strong induction of superoxide-anion production on day 8 of treatment. The kinetics of the effect of aclarubicin on c-myc and c-myb expression were comparable to those associated with the dimethylsulfoxide-induced granulocytic differentiation in this cell line, or to those observed following a chase with actinomycin D, 4 microM. Since aclarubicin partially inhibited total- and poly(A)(+)-RNA synthesis, this macromolecular synthesis inhibition may be causally related to the decrease in c-myc and c-myb mRNA levels. In contrast, the conventional anthracycline doxorubicin, which did not initiate differentiation, failed to affect c-myc or c-myb mRNA levels even in high cytotoxic concentrations, indicating that the suppression of c-myc and c-myb mRNA levels may be an early differentiation-related effect of aclarubicin. On the other hand, actinomycin D, 12.5 nM, and novobiocin, 300 microM, two other known inducers of granulocytic differentiation in HL-60 cells, did not induce an early decrease in c-myb or c-myc expression. Therefore, the immediate suppression of c-myc and c-myb mRNA levels, apparently, is not an obligatory step in chemically induced myeloid differentiation in HL-60 cells, but the common phenomenon in DMSO- and aclarubicin-induced differentiation.
Leukemia 1995 Jan
PMID:DMSO-like rapid decrease in c-myc and c-myb mRNA levels and induction of differentiation in HL-60 cells by the anthracycline antitumor antibiotic aclarubicin. 784 9

Subunit specific radioimmunoassay for aldolase isozymes were developed for the quantification of human aldolase A and B. Aldolase B immunoreactivities were predominantly high in adult normal liver, while aldolase A was distinctly low. Aldolase A was high, while aldolase B was low in neonatal liver compared with the adult liver. Aldolase A immunoreactivities were almost the same as those of aldolase B in fetal liver (28 weeks). Aldolase A was predominantly found in human hepatoma tissues, whereas aldolase B was distinctly low in the same hepatoma tissues. With regard to human hepatoma cell lines, aldolase A was also predominantly found in HepG2 and PLC/PRF/5 cell lines, whereas aldolase B levels were extremely low. Almost the same results were obtained from mRNA expression of aldolase A and B in human hepatoma cell lines by the method of northern hybridization. Effects of various reagents on differentiation of hepatoma cell lines were investigated. Neither Dimethyl Sulfoxide (DMSO) and 12-O-Tetradecanoylphorbol-13-acetate (TPA), which are known to be the inducers of differentiation of human leukemia cell lines such as HL-60, nor Transforming Growth Factor-beta 1 (TGF-beta 1) and Hepatocyte Growth Factor (HGF), which are known to be growth inhibitors, could cause the differentiation of hepatoma cell lines in the alteration of aldolase isozymes. The same data were shown in mRNA expression of aldolase isozymes. These results suggest that aldolase A immunoreactivities and mRNA expression are both predominantly high in hepatoma cell lines, and the reagents such as DMSO, TPA, TGF-beta 1 and HGF which tried to differentiate the hepatoma cell lines used in this study were not effective in the alteration of aldolase isozymes.
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PMID:[Immunoreactivities and messenger RNA expression of aldolase A and B in human hepatoma cell lines]. 786 61

Changes in topoisomerase I (topo I) levels and localization were examined during the course of granulocytic maturation in vitro and in vivo. Western blotting revealed that granulocytic maturation in DMSO-treated HL-60 human leukemia cells was accompanied by a 5-fold decrease in topo I polypeptide content. Consistent with this result, 3- to 5-fold higher concentrations of the topo I poison camptothecin were required to stabilize topo I-DNA adducts in DMSO-treated HL-60 cells compared to untreated cells. Northern blotting revealed that these changes occurred without any decrease in topo I message. Immunolocalization studies revealed that these quantitative changes were accompanied by redistribution of topo I away from the nucleoli, where it was prominently accumulated in untreated HL-60 cells, to a more uniform nuclear distribution in DMSO-treated cells. Similar changes occurred during granulocytic maturation in human marrow in vivo. Western blotting revealed that topo I levels in normal progranulocytes were 50% as high as those in HL-60 cells, levels in metamyelocytes were 35% as high as HL-60 cells, and levels in peripheral blood granulocytes were 5% as high as HL-60 cells. Two other polypeptides that are concentrated in nucleoli, poly(ADP-ribose) polymerase and B23/nucleophosmin, also decreased during the course of granulocytic maturation. These changes were accompanied by an alteration in topo I localization similar to that observed in HL-60 cells during the course of granulocytic maturation. Conversely, treatment of human lymphocytes with the mitogenic lectin concanavalin A resulted in a 3-fold increase in topo I polypeptide content concomitant with a prominent increase in the amount of nucleolar antigen. These observations not only provide a context for understanding the recent observation that topo I levels are higher in human leukemia specimens than in normal marrow but also raise the possibility that elevated topo I levels in other cells might reflect alterations in nucleolar structure and function.
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PMID:Changes in topoisomerase I levels and localization during myeloid maturation in vitro and in vivo. 788 18

Paclitaxel, a novel diterpenoid compound, has been used by dissolving in Cremophor EL (polyoxyethylene castor oil) due to its poor aqueous solubility. Cremophor EL was shown to reverse multidrug resistant phenotypes of various cell lines as well as to reverse cross-resistance to paclitaxel of a multidrug resistant cell line in vitro. Thus, a study was carried out to determine the modifying activity of Cremophor EL on the antitumor activity of paclitaxel against P388 leukemia, adriamycin-resistant subline (P388/ADM) and vincristine-resistant subline (P388/VCR) in vivo. Dimethyl sulfoxide (DMSO) was used as a counterpart solvent. The results showed that, although no significant antitumor activity was observed by paclitaxel in both solvents against P388/ADM, a significantly higher antitumor activity was induced by paclitaxel dissolved in Cremophor EL-based solvent compared with DMSO-based solvent against P388/VCR. However, more significant difference in the antitumor activity of paclitaxel against P388 parental line was observed between two solvents and both resistant sublines showed an obvious cross-resistance to paclitaxel. Therefore, it appeared that cross-resistance reversing activity of Cremophor EL is not so high as to be detectable at in vivo level.
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PMID:[Study for modifying activity of solvents on antitumor activity of paclitaxel]. 790 93

The melanoma differentiation associated gene, mda-6, which is identical to the P53-inducible gene WAF1/CIP1, encodes an M(r) 21,000 protein (p21) that can directly inhibit cell growth by repressing cyclin dependent kinases. mda-6 was identified using subtraction hybridization by virtue of its enhanced expression in human melanoma cells induced to terminally differentiate by treatment with human fibroblast interferon and the anti-leukemic compound mezerein (Jiang and Fisher, 1993). In the present study, we demonstrate that mda-6 (WAF1/CIP1) is an immediate early response gene induced during differentiation of the promyelocytic HL-60 leukemia cell line along the granulocytic or macrophage/monocyte pathway. mda-6 gene expression in HL-60 cells is induced within 1 to 3 h during differentiation along the macrophage/monocyte pathway evoked by 12-0-tetradecanoyl phorbol-13-acetate (TPA) or 1,25-dihydroxyvitamin D3 (Vit D3) or the granulocytic pathway produced by retinoic acid (RA) or dimethylsulfoxide (DMSO). Immunoprecipitation analyses using an anti-p21 antibody indicate a temporal induction of p21 protein following treatment with TPA, DMSO or RA. A relationship between rapid induction of mda-6 gene expression and differentiation is indicated by a delay in this expression in an HL-60 cell variant resistant to TPA-induced growth arrest and differentiation. A similar delay in mda-6 gene expression is not observed in Vit D3 treated TPA-resistant variant cells that are also sensitive to induction of monocytic differentiation. Since HL-60 cells have a null-p53 phenotype, these results demonstrate that p21 induction occurs during initiation of terminal differentiation in a p53-independent manner. In this context, p21 may play a more global role in growth control and differentiation than originally envisioned.
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PMID:Induction of differentiation in human promyelocytic HL-60 leukemia cells activates p21, WAF1/CIP1, expression in the absence of p53. 793 68

Treatment of the human myelomonocytic U937 and THP1 cell lines for 24 h with 180 mM of the differentiation inducer DMSO, resulted in priming these cells to subsequent LPS-induced cytolysis. The observed cytotoxicity was LPS dose-dependent and characterized by a prolonged lag phase with detectable effects only appearing after 8 h. LPS-induced apoptotic cell death in DMSO-pretreated U937 cells as indicated by the appearance of 200 basepair DNA fragments upon agarose gel electrophoresis of total cellular DNA. Furthermore, DMSO pretreatment potentiated the cells' capacity to produce cytokines, especially TNF, upon LPS stimulation. This endogenously present TNF was metabolized by the cells. These observations suggested that the LPS-induced cytostasis/cytotoxicity was mediated through TNF. Indeed, medium conditioned by LPS-stimulated U937-DMSO cells was found to exert a cytotoxic effect on U937-DMSO cells that was completely neutralized by anti-human TNF antiserum. Such TNF-like activities were not only present in the supernatant but also at the level of the cell membrane of LPS-stimulated U937-DMSO cells. Apart from TNF, other exogenously applied recombinant cytokines (IL1, IL6, IFN gamma, GM-CSF) were not cytotoxic to U937-DMSO cells. Thus, DMSO-pretreated myelomonocytic cells become sensitive to LPS-induced cytotoxicity, which is, at least in part, mediated through endogenous TNF.
Leukemia 1994 Nov
PMID:Polar agents with differentiation-inducing capacity prime myelomonocytic cell lines to lipopolysaccharide-induced cytolysis: the role of endogenous tumor necrosis factor. 796 41

The nm23-H1 gene is regarded as a human homologue of the mouse nm23 gene, which was expressed in a non-metastatic subline of mouse melanoma K-1735. The expression levels of nm23-H1 mRNA and the levels of protein during induced differentiation of human leukemia cell lines were analysed. mRNA levels of the megakaryoblastic leukemia line MEG-01, which were induced to differentiate into megakaryocyte by TPA, decreased rapidly from 2 days after the start of treatment and became almost undetectable at day 4. Similar down-regulation of nm23-H1 mRNA was also observed in the induced differentiation of the promyelocytic leukemia line HL-60 by TPA, or DMSO into monocyte-macrophage lineage or granulocytes, respectively. The amount of Nm23-H1 protein was analysed by Western immuno-blot analysis using mouse antiserum raised against a recombinant fusion protein with glutathione S-transferase. The amount of Nm23-H1 protein also decreased during the induced differentiation of these leukemia cell lines. On the other hand, in the differentiation of the erythroleukemia line K562 by hemin, levels of both mRNA and protein of Nm23-H1 elevated transiently, then reduced to the original level. When MEG-01 and K562 were stably transfected with nm23-H1 cDNA, MEG-01 transfectants showed reduced sensitivity to the induction of differentiation, whereas K562 transfectants were better induced to synthesize hemoglobin than controls. These findings suggest the possibility that Nm23-H1 protein plays an important role to maintain the proliferation of immature leukemic cells in MEG-01 and HL-60, but it may also play a role in the early stage of K562 differentiation, possibly in the different manner.
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PMID:Alteration of nm23 gene expression during the induced differentiation of human leukemia cell lines. 805 9

Influence of sera of 15 patients with acute lymphoblastic leukaemia (ALL) and 28 with acute myeloblastic leukaemia (AML) on proliferation and differentiation of human leukaemic cell lines K-562 and HL-60 in a 3 days liquid culture was examined. Differentiation of K-562 cells was measured by the percentage of cells synthesizing Hb, and HL-60 cells by the percentage of cells with positive NBT test and positive NSE activity. Additionally the influence of differentiation inducers such as hemin for K-562 and DMSO and TPA for HL-60 was examined. It has been found that sera of patients with ALL and AML inhibit the proliferation of K-562 and HL-60 cells, induce the differentiation of K-562 cells, but inhibit the induction of differentiation by hemin. The sera of the examined patients inhibit the differentiation of HL-60 into granulocytes and monocytes, but do not affect the differentiation induced with DMSO and TPA.
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PMID:[Influence of patients' sera in acute leukemia on proliferation and differentiation of K-562 and HL-60 cells in liquid culture]. 806 89

Myelodysplastic syndrome (MDS)-derived leukemia cell line P39/Tsugane could be induced to apoptosis by a variety of agents including metabolic inhibitors, a calcium ionophore and differentiation-inducing agents. As evaluated by characteristic morphological changes and oligonucleosomal lengths DNA ladder, the levels of apoptosis in P39 cells induced by actinomycin D, or A23187, were far greater than in other myeloid lines examined in this study. When 22-oxa-1 alpha, 25(OH)2D3 (D3), dimethyl sulfoxide (DMSO) and all-trans retinoic acid (RA) were used as differentiation-inducers, varying degrees of apoptosis were seen. D3 induced monocytoid differentiation, but not apoptosis above the control level. On the other hand, RA induced profound apoptosis concomitant with the progressive expression of differentiation markers. Studies on morphology, functions and phenotypes of P39 cells exposed to differentiation inducers suggest that the incidence of apoptosis was not affected by the process of differentiation, but cells in the process of varying degrees of differentiation may die via apoptosis. Moreover, RA-treated P39 cells are unique in the simultaneous occurrence of profound apoptosis and differentiation. We propose that RA-treated P39 differentiation model is ideally suited for the study of MDS.
Leukemia 1994 Mar
PMID:Marked apoptosis of human myelomonocytic leukemia cell line P39: significance of cellular differentiation. 812 49


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