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)

Tumour necrosis factor (TNF) affects the growth of human leukaemic cells by different modes of action depending on the type of leukaemia involved. We have analysed the structure of TNF receptors on cells from different types of leukaemia, including acute lymphoblastic leukaemia (ALL), acute myeloblastic leukaemia (AML), chronic lymphocytic leukaemia (CLL), and chronic myelocytic leukaemia (CML) either in chronic phase (CML-CP) or blastic crisis (CML-BC). The affinity crosslinking technique showed the existence of TNF receptors on cells from all the leukaemic cases studied with similar receptor structures. The TNF receptor showed a molecular weight of 76 kD when examined by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. In conclusion, we provide evidence for existence of TNF receptors on several types of human leukaemia cells with an apparent molecular weight of 76 kD. Apparently, the discrepancy of TNF actions on the leukaemic growth are not related to the structure of TNF receptors.
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PMID:Analysis of the TNF receptors on human leukaemia cells by affinity cross-linking. 132 64

Changes of intracellular ionic homeostasis are believed to play a role in the cytostatic action of cis-DDP. It has been observed by means of X-ray microanalysis that cis-DDP did not alter the intracellular Na+/K(+)-ratio of K 562 leukemia cells during incubation periods which lasted shorter than the average doubling time of the cells of nearly 15 h. After 24 h the treated cells displayed at least two main populations in the distribution histogram of the Na+/K(+)-ratio. The results indicated that the passage of cis-DDP through the plasma membrane by itself did not change the monovalent electrolyte balance at the early stage of its action in K 562 cells.
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PMID:Effect of cis-diaminedichloroplatinum (II) (cis-DDP) on the intracellular Na+/K(+)-ratio in K 562 leukemia cells as revealed by X-ray microanalysis. 133 93

Anthracycline accumulation was evaluated by flow cytometry or radiolabeled drug assays in cells and cytoplasts (enucleated cells) prepared from parental and multidrug-resistant human K562 leukemia cells. Treatment with energy inhibitors, such as dinitrophenol (DNP) or sodium azide/deoxyglucose, led to a marked decrease in daunorubicin accumulation in parental cells and cytoplasts. Another ionophore, monensin, also caused a significant decrease in daunorubicin accumulation; however, ATPase inhibitors ouabain, vanadate, and N-ethylamaleimide had little or no effect. The lysosomatropic agents chloroquine and methylamine caused a moderate decrease in anthracycline accumulation. Fluorescence microscopy showed that the DNP-sensitive daunorubicin uptake occurred in a nonnuclear subcellular compartment. Studies using increasing daunorubicin concentrations demonstrated fluorescence quenching that occurred in the nonnuclear, DNP-sensitive compartment. The effect of inhibitors on the accumulation of rhodamine 123 and acridine orange strongly implicated lysosomes as the principal compartment of this inhibitable daunorubicin accumulation. Cytoplasts from P-glycoprotein containing multidrug-resistant K562 cells demonstrated a verapamil-reversible, decreased daunorubicin accumulation that was observed in resistant whole cells. Verapamil pretreatment of cytoplasts from resistant cells revealed the subcellular DNP-sensitive uptake present in parental cytoplasts. These studies demonstrate that cytoplasts are an effective means to study drug transport in mammalian cells without nuclear drug binding. Parental K562 cells and cytoplasts exhibit an energy-dependent accumulation of daunorubicin into cytoplasmic organelles that is also present in resistant cells and cytoplasts when P-glycoprotein mediated efflux is inhibited.
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PMID:Energy-dependent accumulation of daunorubicin into subcellular compartments of human leukemia cells and cytoplasts. 135 Feb 80

Standard anti-leishmanial drugs were tested for their ability to inhibit the growth of intracellular amastigotes of Leishmania aethiopica, L. donovani and L. infantum in the human leukemia monocyte THP-1 cell line. Sodium stibogluconate and meglumine antimoniate were active against L. donovani with ED50 values of 8.9 micrograms SbV/ml and 2.9 micrograms SbV/ml, respectively. L. aethiopica was less sensitive to sodium stibogluconate with an ED50 value of 25.3 micrograms SbV/ml while pentamidine had an ED50 value of 0.6 microM. Both L. donovani (ED50, 9.3 microM), and L. aethiopica (ED50, 6.4 microM), were sensitive to aminosidine sulphate. An L. infantum isolate, clinically resistant to meglumine antimoniate treatment, had an ED50 of 22.2 micrograms SbV/ml. The toxic level of drugs on host cells was determined by colorimetric Methyl Tetrazolium (MTT) assay prior to activity tests. The results obtained with the THP-1 in vitro drug screening model were similar to those obtained in the mouse peritoneal macrophage model.
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PMID:An in vitro model for screening antileishmanial drugs: the human leukaemia monocyte cell line, THP-1. 135 51

Transforming growth factor-beta 1 (TGF-beta 1) induces cell death in myeloid leukemia by apoptosis. In the M1 myeloid leukemia, this induction of apoptosis was inhibited by granulocyte colony-stimulating factor (G-CSF) or interleukin-6 (IL-6) and to a lesser extent by IL-1 alpha. IL-3 and stem cell factor/mast cell growth factor (SCF) showed only a marginal effect, and granulocyte-macrophage and macrophage CSFs (GM-CSF and M-CSF, respectively) were inactive. The induction of apoptosis by TGF-beta 1 in a different myeloid leukemia (7-M12) was inhibited by GM-CSF and IL-3 but not by the other cytokines. In the absence of TGF-beta 1, both M1 and 7-M12 leukemic cells were independent of hematopoietic cytokines for cell viability and growth. The cytotoxic compounds vincristine, vinblastine, adriamycin, cytosine arabinoside, cycloheximide, and sodium azide, some of which are used in cancer chemotherapy, induced cell death by apoptosis in both leukemias. As with TGF-beta 1, apoptosis induced by these cytotoxic compounds was inhibited by GM-CSF (7-M12 leukemia) and by G-CSF or IL-6 (M1 leukemia). Cyclosporine A decreased cell multiplication in M1 cells without inducing apoptosis, and G-CSF and IL-6 inhibited the cytostatic effect of cyclosporine A. It is suggested that the clinical use of cytokines to correct therapy-associated myelosuppression should be carefully timed to avoid protection of malignant cells from the cytotoxic action of the therapeutic compounds.
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PMID:Hematopoietic cytokines inhibit apoptosis induced by transforming growth factor beta 1 and cancer chemotherapy compounds in myeloid leukemic cells. 138 3

The effect of selenite coadministration on the toxicity and antitumor activity of repeated treatment with high doses of cis-diamminedichloroplatinum (cis-DDP) was examined in mice. Sodium selenite was injected s.c. into separate abdominal sites of mice together with cis-DDP at a molar ratio of 1:3.5 (selenite to cis-DDP) on day 0. The same amount of selenite was given daily for 4 subsequent days (days 1-4). This fixed administration schedule was repeated weekly for a total of 7 weeks. Under the experimental conditions used, the lethal toxicity, renal toxicity [indicated by an increase in blood urea nitrogen (BUN) and plasma creatinine levels], hepatic toxicity (indicated by an increase in plasma GPT and GOT activity), and myelotoxicity (indicated by a decrease in the numbers of leukocytes and platelets) observed in mice given repeated doses of cis-DDP alone (15 or 25 mumol/kg, s.c.) were significantly depressed by the coadministration of sodium selenite. Treatment with cis-DDP alone (15, 20, or 25 mumol/kg, s.c.) resulted in some dose-dependent prolongation of the life span of mice transplanted either s.c. with colon adenocarcinoma 38 (colon 38) or i.p. with P388 leukemia (P388) but did not completely depress the tumor growth, and the animals died of either progressive disease or cis-DDP-induced toxicity. However, following the coadministration of 7.1 mumol/kg selenite with 25 mumol/kg cis-DDP, all of the mice transplanted either s.c. with colon 38 or i.p. with P388 survived for as long as 4 months after the end of the treatment and showed no evidence of malignancy. These results indicate that selenite coadministration enables the use of increasing doses of cis-DDP and, consequently, enhances the antitumor effect of cis-DDP by depressing its side effects.
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PMID:Effect of coadministration of selenite on the toxicity and antitumor activity of cis-diamminedichloroplatinum (II) given repeatedly to mice. 139

Murine promonocytic leukemias involving insertional mutagenesis of the c-myb locus can be induced by replication-competent retroviruses. In previously studied promonocytic leukemic cells induced by Moloney murine leukemia virus (called MML), the provirus has been invariably integrated upstream of exons 3 or 4 and the leukemic cells expressed aberrant RNAs with fused virus-myb sequences. Furthermore, Myb expressed by these cells has been shown to be truncated by 47 or 71 amino acids. The present report examines the mechanisms of myb activation in leukemias induced by two other retroviruses, amphotropic virus 4070A and Friend strain FB29 (the leukemias are called AMPH-ML and FB-ML, respectively). This study revealed two additional c-myb proviral insertion sites in these promonocytic leukemias. One FB-ML had a proviral integration in exon 9, and expressed a C-terminally truncated Myb protein of 47 kDa similar to that previously demonstrated to be expressed in the myelomonocytic cell lines NFS60 and VFL-2. However, a sequence of reverse-transcribed and amplified RNA from this leukemia demonstrated that the truncation involved a loss of 248 amino acids compared with a loss of 240 amino acids in the myelomonocytic cell lines. Another leukemia had a provirus integrated in the 5' end of c-myb upstream of exon 2 (in the first intron) and produced a Myb protein that was indistinguishable on sodium dodecyl sulfate-polyacrylamide gel electrophoresis from normal Myb. This latter leukemia (FB-ML R1-4-10) expressed Myb with the smallest N-terminal truncation observed so far in promonocytic leukemias; translation begins at an ATG within c-myb exon 2, leading to loss of only 20 amino acids from the N terminus. Unlike the proteins produced in Moloney murine leukemia virus-induced promonocytic leukemias (MML) that have larger truncations, this protein has an intact DNA binding region and does not contain N-terminal amino acids encoded by gag. However, this protein is similar to all N-terminally truncated Mybs so far studied, in that the truncation resulted in deletion of a casein kinase II phosphorylation site which has been proposed to be involved in regulation of DNA binding.
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PMID:New sites of proviral integration associated with murine promonocytic leukemias and evidence for alternate modes of c-myb activation. 152 51

Western blot analysis of HTLV-I virus particles from HUT-102 cells revealed a 40-kD protein strongly reactive with Tax-specific rabbit antisera. This protein subsequently was isolated from density gradient purified virions by preparative sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), purified from comigrating Gag and human cellular proteins by reversed-phase high-performance liquid chromatography (HPLC) and identified as the tax-encoded gene product by amino acid composition analysis. Among extracellular virions from five HTLV-I producing cell lines, only those from HUT-102 and C10MJ cells contained a detectable Tax protein, although all cells expressed Tax mRNA and protein intracellularly. To investigate the diagnostic implications of virion-associated Tax protein, sera from HTLV-I-infected individuals were compared on HUT-102 and MT-2 virus Western blots. The seroprevalence of antibodies to Tax, but not Gag or Env proteins, was substantially higher among adult T-cell leukemia and tropical spastic paraparesis patients using HUT-102 viral proteins. Thus, immunoassays utilizing HUT-102 virus are most sensitive for detection of Tax-reactive antibodies.
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PMID:Virion-associated trans-regulatory protein of human T-cell leukemia virus type I. 154 Apr 9

1,25-Dihydroxyvitamin D3 (1,25-(OH)2D3)-induced differentiation of HL-60 leukemia cells is accompanied by a number of cellular changes including regulation of oncogene expression and induction of terminal differentiation. We investigated the mechanism by which 1,25-(OH)2D3 induces these changes. We detected 10 nuclear phosphoproteins, designated p66, p45, p36, p33, p32, p27, p22, p19, p18 and p17, that show alterations in phosphorylation within 6-40 h of 1,25-(OH)2D3 treatment. When phosphorylation reactions were performed with isolated nuclei (in vitro), three of these proteins were phosphorylated in a calcium and phospholipid dependent manner: p66, p36, and p19 P66 was phosphorylated in response to 1,25-(OH)2D3 and purified in a manner similar to that used for nuclear lamins. Western blot analysis of 2-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) gels confirmed its identity as lamin B. Phosphorylation of p17 and p18 decreased following 1,25-(OH)2D3 treatment. We separated p17 and p18 by SDS-PAGE and obtained N-terminal amino acid sequence to identify these phosphorproteins as histones H2b and H3, respectively. P19 and p22 were both DNA-cellulose binding proteins whose phosphorylation was altered by 1,25-(OH)2D3 treatment. Increased phosphorylation of p27 was detected using 2-dimensional SDS-PAGE. Phosphorylation of nuclear proteins in the intact cell (in vivo), revealed increases in p66, p45, p36, and p33 phosphorylation and a decrease in p17 phosphorylation following 1,25-(OH)2D3 treatment. We detected an increase in phosphorylation of p32, which was extracted with salt from nuclei and migrated on SDS-PAGE similar to histone H1. Thus, we have identified 1,25-(OH)2D3-sensitive nuclear phosphoproteins, including lamin B and several histones. We have also detected and characterized several less abundant nuclear DNA binding phosphoproteins whose phosphorylation was affected by 1,25-(OH)2D3.
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PMID:Identification of lamin B and histones as 1,25-dihydroxyvitamin D3-regulated nuclear phosphoproteins in HL-60 cells. 155 89

The influence of a commercial formulation of 5-fluorouracil (5-FU) on the stability and pharmacological properties of two platinum derivatives, cisplatin and carboplatin, was studied to determine whether the drugs could be mixed in containers or intravenous lines. When cisplatin was incubated in a French commercial formulation of 5-FU (Fluoro-uracile, Roche, France), high-performance liquid chromatographic (HPLC) studies demonstrated a rapid disappearance of the parent platinum compound, the extent of the degradation being 75% after 3.5 h. These studies also revealed that the degradation was not caused by a reaction between 5-FU and cisplatin but rather resulted from an interaction between cisplatin and trometamol, the excipient used in the French 5-FU formulation to buffer the solution at pH 8.2. The sole presence of trometamol in a cisplatin solution for 24 h at 30 degrees C resulted in the complete inhibition of both the ability of cisplatin to bind in vitro to human serum albumin and the antitumor activity of the cytostatic agent against P388 leukemia in mice (T/C% = 88% for cisplatin+trometamol vs greater than 333% for cisplatin). When cisplatin was incubated at the same pH in trometamol-free sodium hydroxide solutions (the excipient used in 5-FU formulations in several countries, including the United States and the United Kingdom), the parent compound was transformed into reactive species that were toxic to mice (T/C% = 40% in P388 leukemia). The degradation determined for a carboplatin-trometamol admixture using HPLC was similar to that found for cisplatin but occurred at a slower rate (0 after 3.5 h incubation and 55% after 24 h). The antitumor activity of carboplatin in P388-bearing mice was not significantly altered by a 24-h period of preincubation in the presence of trometamol (T/C% = 209% vs 241% for treatment with carboplatin in the absence of trometamol). As in the case of cisplatin, incubation of carboplatin for 24 h in a sodium hydroxide solution resulted in a toxic effect (T/C% = 64%). Our results thus demonstrate the incompatibility of both cisplatin and carboplatin with commercial formulations of 5-FU.
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PMID:Modification of the physicochemical and pharmacological properties of anticancer platinum compounds by commercial 5-fluorouracil formulations: a comparative study using cisplatin and carboplatin. 156 89


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