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)

Azelaic acid has been shown to have a dose- and time-dependent inhibitory effect on both proliferation and cell viability of murine and human melanoma cells at a concentration of 10(-3) M and higher. It also has an inhibitory effect on DNA synthesis and plasminogen activator activity, and causes swelling and vacuolation of mitochondria. These effects have also been observed with other tumoral cells in culture-lymphoma and leukaemia derived cell lines, and human squamous cell carcinoma. Normal cells in culture are not generally affected by exposure to azelaic acid. Tissue culture experiments have confirmed the clinical activity and efficacy of azelaic acid, and biochemical conclusions as to its mode of action.
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PMID:Hyperpigmentary disorders--mechanisms of action. Effect of azelaic acid on melanoma and other tumoral cells in culture. 267 85

We present the case of a young man with acute monocytic leukemia (French-American-British classification:M5) and systemic hyperfibrinolysis with severe bleeding. Although fibrinolysis is usually mild and secondary to disseminated intravascular coagulation, its role as a primary and dominant factor in rare cases of leukemia warrants that its presence be sought as a cause of abnormal bleeding. Decreased serum plasminogen and increased serum plasmin determined by synthetic substrate assay and a negative protamine paracoagulation test are crucial findings. Use of high-dose epsilon-aminocaproic acid was effective in treating this complication. A transient increase in fibrinolytic activity coincident with the early effect of antileukemic treatment suggested that plasminogen activator and/or fibrinolytic protease substances were released from leukemic cells. Fibrinolytic activity subsequently disappeared with reduction in the population of leukemic cells.
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PMID:Primary fibrinolysis in acute monocytic leukemia. 276 88

The effects of maturation inducing agents on the production of plasminogen activator (PA) and plasminogen activator inhibitor (PAI) by the human promyelocytic leukemia cell line HL-60 were examined. PA activity, which was calibrated with a urokinase standard, was 3-6 mU/10(6) cells when measured in supernatants from control cells. This activity increased at least two-fold after dimethylformamide (DMF) or retinoic acid (RA) was added to cell cultures, and as much as ten to thirty-fold when cells were exposed to 12-O-tetradecanoylphorbol-13-acetate (PMA), an agent that induces monocytoid differentiation in HL-60 cells. The PA activity produced by control and induced cells had the same molecular weight as urokinase (UK), and was completely inhibited by antibodies to UK. Cells that were induced with PMA but not with RA or DMF also produced an inhibitor to UK that was identified as PAI-2, the plasminogen activator inhibitor that is produced by monocytes. Because of its dual capacity to produce both UK and PAI, the HL-60 cell line represents a useful model for studies of the fibrinolytic mediators that are generated and released by leukemia cells.
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PMID:Stimulated production of urokinase and plasminogen activator inhibitor-2 by the human promyelocytic leukemia cell line HL-60. 314 93

Two short-lived vitamin K-dependent factors, factor VII and protein C, were measured by both functional and antigenic techniques in 3 hematological conditions known for their risk of hepatotoxicity: Following use of asparaginase and bisantrene, and patients at high risk of hepatic veno-occlusive disease after allogenic bone marrow transplantation for relapse of acute leukemia of accelerated phase of evoluted chronic myelogenic leukemia. In these 3 conditions functionally measured levels of protein C and factor VII, and antigenically measured levels of both these factors proved to be early markers of incipient hepatic involvement. These tests were easy to use routinely were reproducible, and proved to be predictive of veno-occlusive disease in grafted patients at the preconditioning stage. In the follow-up of bone marrow grafted patients plasma markers of endothelial function (von Willebrand's factor, tissue type plasminogen activator, and plasma activity of angiotensin converting enzyme) were significantly altered at the time of overdose with cyclosporin A, probably due to a drug-induced in vivo lesion of the endothelium. In the search for cytoprotective drugs for the prevention of veno-occlusive disease in bone marrow grafted patients prostaglandin E1 (PGE1) was given prior to and for at least 4 weeks after transplantation and proved to be effective by biological criteria (the level of protein C mainly). This deserves further study in a prospective clinical trial of the potential usefulness of PGE1 in preventing liver veno-occlusive disease in bone marrow grafted patients.
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PMID:[Hemostasis tests as markers of hepatic and endothelial toxicity in chemotherapy]. 329 Aug 34

Cells of the myelomonocytic leukemia cell line RC-2A were studied for their ability to synthesize clotting-promoting and fibrinolytic factors. The cells were observed to generate procoagulant activity (PCA) in readily measurable quantities. Incubation of RC-2A cells with phorbol myristate acetate (PMA; 3 ng/ml) or phytohemagglutinin (PHA, 10 micrograms/ml) for 18 h resulted in a 4-5-fold increase in PCA relative to unstimulated control. The PCA of RC-2A cells was tissue factor-like in that it was dependent on factor VII but not on factors VIII or IX. RC-2A cells also produced plasminogen activator (PA). Secreted PA was approximately 70% of the PA of an identical number of human monocyte-derived macrophages; fresh isolated monocytes synthesized virtually no PA. Compared to macrophages, RC-2A cells secreted less or no PA-inhibitors. Lysates of RC-2A cells contained over three times more PA than lysed macrophages. Stimulation of the cells with lectins (PHA, concanavalin A) or PMA was followed by a modest (2-3-fold) increase in PA. Enzyme immunoassay with antibodies to urokinase (u-PA) or tissue-type PA (t-PA) identified the RC-2A plasminogen activator as being of urokinase type.
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PMID:Cells of the human myelomonocytic line RC-2A synthesize tissue factor-like procoagulant and urokinase-type plasminogen activator. 329 13

Guanidinobenzoatase is a proteolytic enzyme capable of degrading fibronectin and is a tumour associated enzyme. Guanidinobenzoatase has been shown to be an arginine selective protease and is distinct from trypsin, plasminogen activator, plasmin, thrombin and a newly described tumour associated enzyme specific for guanidino phenylalanine residues. These conclusions have been derived from inhibition studies employing 4-methyl-p-guanidinobenzoate as substrate. Three active site titrants for trypsin have been shown to be good substrates for guanidinobenzoatase. A new active site titrant for trypsin, rhodamine bisguanidinobenzoate, can also be used to assay guanidinobenzoatase in a stoichiometric manner. This active site titrant can be employed to label guanidinobenzoate on the surface of leukaemia cells.
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PMID:Further inhibition studies on guanidinobenzoatase, a trypsin-like enzyme associated with tumour cells. 333 44

While studying the effects of chemotherapy on glucocorticoid receptor (GR) binding levels in hematological malignancies, we observed a sizable increase in nuclear GR binding of [3H]dexamethasone in peripheral leukocytes from a chronic basophilic leukemia patient following treatment with hydroxyurea plus prednisone, but not after prednisone alone. This apparent clinical effect of hydroxyurea led to an examination of hydroxyurea effects on GR binding and sensitivity in the glucocorticoid-sensitive human lymphoblast cell line GM4672A. GR binding levels in GM4672A cells were measured following a 3-day exposure to 50 microM hydroxyurea, a concentration chosen to have a minimal but measurable effect on cellular growth rates with little or no effect on cellular viability. Under these conditions, nuclear [3H]dexamethasone receptor binding measured by Scatchard analysis using a whole-cell assay was elevated 2.4-fold over control values (P less than 0.05), while cytosolic residual receptor binding (measured at 37 degrees C) remained unchanged. Thus, the total cellular content of measurable GR was increased, and this increase was totally accounted for by GR capable of nuclear binding. Hydroxyurea treatment of GM4672A cells had no effect on the affinity of nuclear or cytosolic GR for [3H]dexamethasone. The increase in measurable nuclear-bound receptors occurred in a time-dependent manner over a period of 3 days and was fully reversible within 3 days following removal of hydroxyurea. The increase in receptor binding could not be explained by the slight alterations in cell cycle kinetics which occur at this low level of hydroxyurea. Despite increased receptor binding, cellular glucocorticoid responsiveness was unaltered as assessed by dexamethasone inhibition of cell growth and dexamethasone inhibition of a urokinase-like plasminogen activator. Thus, increased nuclear and total cellular GR binding levels in hydroxyurea-treated GM4672A cells are not associated with increased glucocorticoid responsiveness.
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PMID:Elevated glucocorticoid receptor binding in cultured human lymphoblasts following hydroxyurea treatment: lack of effect on steroid responsiveness. 373 Oct 65

The expression of plasminogen activator activity (PA) by L1210 leukemic ascitic cells, obtained from the peritoneum of BDF1 mice, increases in the terminal stages of the disease. Treatment of mice carrying advance leukemia (day 6 following inoculation with 10(6) cells i.p.) with 6-azauridine (AzUR) results in prolonged survival (2-3 days) and also in increased expression of PA activity by the ascitic cell population. Similar treatment with pyrazofurin (PF), another inhibitor of orotidylate decarboxylase and of de novo pyrimidine synthesis, fails to produce either of these effects. Neither AzUR or PF, given at the early stage of tumor growth (day 3), extend the life span nor do they cause increase of the PA activity. Thus, the elevation in PA activity following treatment with AzUR is associated with the asymptotic stage of the disease and this phenomenon correlates positively with the life-prolonging effects of this drug. An analysis of the PA activity elicited by intact cells, secretions, and cellular digests suggests that most of the activity originates on the surface of the cells. The results indicate that the described in vivo effect of AzUR, but not that of PF, on late-stage leukemia, is mediated by the changes in the fibrinolytic potential of the tumor or host cells rather than through the inhibition of the de novo pyrimidine synthesis.
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PMID:Effect of 6-azauridine and pyrazofurin on fibrinolysis by L1210 leukemic cells. 617 11

We attempted to examine procoagulant activity (PCA), X activator activity (XAA) and plasminogen activator activity (PlgAA) of various leukemic cell lysates: 17 acute myelocytic leukemias (AML), 4 acute promyelocytic leukemias (APL), 9 acute myelomonocytic leukemias (AMMoL), 7 chronic myelocytic leukemias (CML), 4 CML with blastic crisis, 7 T cell acute lymphocytic leukemias (ALL), 8 adult T cell leukemias (ATL), 8 null cell ALL, 6 B cell lymphocytic leukemias. Among those 70 cases, 4 APL, 4 AMMoL and 5 AML were associated with overt disseminated intravascular coagulation (DIC) and 5 T cell ALL, 7 ATL and 2 null cell ALL were associated with hypofibrinogenemia not adapted for DIC. The sample used was the lysate of 10(7) cells. PCA was measured by recalcification time of normal plasma with the cell lysate, XAA and PlgAA was measured by chromogenic substrate. APL and AML, especially those associated with overt DIC, had high PCA, and lymphocytic leukemia generally had low PCA in comparison with normal controls. Total PCA (PCA multiplied by cell count/microliter) was remarkably increased in DIC and mildly increased in ALL with hypofibrinogenemia. The change in XAA and total XAA (XAA multiplied by cell count/microliter) was not remarkable in any leukemia except for T cell ALL and null cell ALL with hypofibrinogenemia. PlgAA was high in lymphocytic leukemias with hypofibrinogenemia, APL and AMMoL with DIC. Total PlgAA (PlgAA multiplied by cell count/microliter) was high especially in T cell ALL and null cell ALL with hypofibrinogenemia. Thus it is probable that PCA is the most important factor causing DIC in myelogenous leukemia and that PlgAA is the most important factor causing hypofibrinogenemia in lymphocytic leukemia. The measurement of these activities in the leukemic cells is valuable in prediction and prevention of the hemostatic disorder in leukemia.
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PMID:Coagulant and fibrinolytic activities in the leukemic cell lysates. 635 39

HeLa cells incubated with 12-O-tetradecanoylphorbol-13-acetate (TPA), and rat basophilic leukemia (RBL-1) cells incubated with calcium ionophore, showed increased levels of the protease plasminogen activator. These treatments have previously been shown to stimulate the cellular metabolism of arachidonic acid. The induction of plasminogen activator in both cell types was inhibited in a dose-dependent manner by 5,8,11,14-eicosatetraynoic acid and nordihydroguaiaretic acid, two compounds known to inhibit arachidonate metabolism via lipoxygenases. In contrast, indomethacin, which selectively inhibits arachidonate metabolism via cyclooxygenase, was inactive. The levels of four enzyme markers in HeLa cells were unchanged by treatment with TPA plus the lipoxygenase inhibitors, indicating that the inhibitors did not exert their effects on plasminogen activator via general cell toxicity. HeLa cells preincubated with [3H]arachidonate and subsequently challenged with TPA produced small amounts of material with the chromatographic mobilities and resistance to indomethacin expected of hydroxylated fatty acids derived via lipoxygenase. RBL-1 cells have been shown previously to produce leukotrienes and other lipoxygenase metabolites when treated with calcium ionophore. Plasminogen activator in HeLa cells was stimulated by up to 2.5-fold by incubation with 0.5-2 micrograms/ml 5-hydroxyeicosatetraenoic acid. Our results suggest that the induction of plasminogen activator in HeLa and RBL-1 cells is not mediated by prostaglandins or thromboxanes, but may be mediated or modulated by arachidonate metabolites derived via a lipoxygenase pathway.
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PMID:Induction of plasminogen activator by 12-O-tetradecanoylphorbol-13-acetate and calcium ionophore. Suppression by inhibitors of fatty acid lipoxygenase. 640 51


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