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)

Plasma levels of urokinase-type plasminogen activator (u-PA) were measured with an enzyme-linked immunosorbent assay in patients with leukemias. As compared with healthy subjects (0.73 +/- SD 0.17 ng/ml), plasma u-PA antigen level was markedly elevated in patients with acute promyelocytic leukemia (APL) (1.76 +/- 0.89 ng/ml) at disease onset. Mean u-PA concentrations in patients with other acute nonlymphoblastic leukemia (0.57 +/- 0.51 ng/ml), acute lymphoblastic leukemia (0.77 +/- 0.82 ng/ml) and chronic myelocytic leukemia in blastic crisis (1.30 +/- 1.35 ng/ml) were not significantly elevated, but some of them showed an elevation of plasma u-PA. Plasma u-PA values were correlated with some of the fibrinolytic parameters such as FDP and D-dimer. Plasma u-PA antigen was decreased after the administration of antileukemic drugs in patients with APL. These results suggest that the coagulopathy in patients with various leukemias may in part be associated with u-PA release from the leukemic cells, especially in patients with APL.
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PMID:Plasma urokinase-type plasminogen activator in patients with leukemias. 787 8

We previously reported that urokinase (uPA) is produced by the human prostate cancer cell line, PC-3, and could function as a growth factor for cells of the osteoblast phenotype. To examine the role of uPA in metastasis to the skeleton and to extraskeletal sites, we have developed a homologous model of uPA overexpression in a rat prostate cancer cell line. Full length cDNA encoding rat (r) uPA was isolated and subcloned as a 1.4-kilobase XbaI-BspHI fragment in the sense and antisense orientation into the Moloney murine leukemia retroviral vector pYN. The control (pYN) and experimental (pYN-ruPA, pYN-ruPA-AS) plasmids were transfected into Dunning R 3227, Mat LyLu rat prostate carcinoma cells. Experimental clones expressing at least 5-fold higher (pYN-ruPA) or 3-fold lower (pYN-ruPA-AS) than controls were selected, and control and experimental cells were inoculated into the left ventricles of inbred male Copenhagen rats. Animals were sacrificed at timed intervals to examine the evolution of metastatic lesions. Control animals developed metastases to the lumbar vertebrae resulting in spinal cord compression and hind limb paralysis at 20-21 days postinoculation. Animals inoculated with cells overexpressing uPA developed hind limb paralysis significantly earlier (by day 14-15 postinoculation). Additionally, more widespread skeletal (ribs, scapula, and femora) metastases were seen. Serum from experimental animals showed a progressive elevation in alkaline phosphatase levels, and histological examination of lumbar metastases revealed markedly increased osteoblastic activity over that observed in control animals. In contrast to this, animals inoculated with cells underexpressing uPA developed hind limb paralysis significantly later (days 25-29 postinoculation) and displayed decreased tumor metastasis. These studies support a role for the catalytic domain of uPA in enhancing both skeletal and nonskeletal prostate cancer invasiveness and are consistent with a role for the growth factor domain of uPA in mediating an osteoblastic skeletal response.
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PMID:Urokinase overproduction results in increased skeletal metastasis by prostate cancer cells in vivo. 816 83

Two cases of invasive aspergillosis are reported. Case 1, a 3-year-old boy with leukemic transformation of myelodysplastic syndrome, had an aspergillus infection in the hand, resulting in necrosis of the thumb. Case 2, an 18-year-old girl with acute megakaryoblastic leukemia, had an aspergillus skin infection on the wrist, accompanied by swelling and discoloration of the arm. In Case 2, angiography revealed a hypovascular lesion and vascular irregularity, suggesting that vessels were involved. Intraarterial infusion of urokinase and amphotericin B led to improvement of these symptoms in this patient. The combination of urokinase and an antifungal drug should be considered for intractable aspergillus infections involving the extremities.
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PMID:Invasive aspergillosis in leukemic children. 831 73

We have examined the mononuclear cell fraction from 35 individuals, 18 with hematologic malignancies and 17 healthy controls for the presence of cell surface-associated plasminogen activator (PA) activity. PA activity was found on the cell surface of 10 out of 12 samples from patients with acute leukemia. In addition to active urokinase (uPA) found on the cell surface in four out of five acute myeloid leukemia patients, tissue-type PA activity was detected in the same samples (3 of 5). Two out of four samples from acute lymphoid leukemia displayed only uPA activity and three out of three samples from biphenotypic leukemia were also clearly uPA-positive. Plasmin activity was not detected in any of the samples. PA activity was not found on the surface of mononuclear cells from either patients with chronic lymphoid leukemia or healthy controls and, in this respect, the cell surface-bound uPA activity behaved as a marker for acute leukemia. The finding of PA activity on the cell surface in acute leukemia suggests that there may be continuous generation of plasmin with consequent consumption of plasma plasmin inhibitors.
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PMID:Abundant urokinase activity on the surface of mononuclear cells from blood and bone marrow of acute leukemia patients. 833 54

Human leukemia cell lines, unlike those from adherent tumors, have been shown to continuously activate the pro-urokinase (pro-u-PA) they produce. In the present study we found that, in normal cell-culture conditions in 10% FCS the plasminogen activation cascade works continuously on monocytoid leukemia cells, which expressed plasmin activity and active u-PA on their cell surface. This plasmin catalyzed the conversion of the produced pro-u-PA to active 2-chain urokinase (tcu-PA), and was derived from bovine serum plasminogen by the activity of cell-bound tcu-PA. Plasmin generation was abolished and pro-u-PA accumulated in cell cultures that were grown for several days, either in the presence of serum thoroughly depleted of plasminogen, or in the presence of 1 mM tranexamic acid. Plasmin generated on the cell surface was found to be present in 2 enzymatically active fragments, of M(r) 85,000 and M(r) 50,000, which were slowly released into the growth medium. These fragments could activate pro-u-PA in serum-free growth medium. Most of the bound plasmin could be washed off cells with 10 mM tranexamic acid, but complete removal of plasmin from the cell surface required washing of the cells with acid-glycine pH 3.0.
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PMID:Persistence of plasmin-mediated pro-urokinase activation on the surface of human monocytoid leukemia cells in vitro. 842 1

Plasminogen activator (PA) and PA inhibitor (PAI) were measured in homogenates of leukemia cells. Both PA and PAI levels were higher in non-lymphoblastic leukemia than in lymphoblastic leukemia. The levels were below the sensitivity of determination in chronic myelocytic leukemia (CML) but showed significant increases in blast crisis (CML,bc). The level of the tissue type PA (t-PA) antigen was highest in acute myeloblastic leukemia (AML) and that of the urokinase type PA (u-PA) was highest in acute promyelocytic leukemia (APL). The PAI-I antigen showed no marked cell specificity, but the PAI-II antigen was markedly increased in myelomonocytic leukemia and acute monocytic leukemia (AMoL). From these findings, various PAs and PAIs are considered to be present in leukemia cells and to be involved in hemostatic disorders, thus they are of diagnostic value in leukemia.
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PMID:Plasminogen activators and their inhibitors in leukemic cell homogenates. 843 77

This work provides evidence that the production by monocytes of hepatocyte stimulating factor(s) for fibrinogen biosynthesis was dramatically increased when monocytes were exposed to Adriamycin. This effect was related to an increased production of leukaemia inhibiting factor (LIF), a cytokine known to stimulate fibrinogen biosynthesis by hepatic cells. Adriamycin also induces an increase in membrane-associated urokinase on monocytes. These results are consistent with the clinical observation in patients with ovarian cancer that when the CA-125 tumour marker decreases during chemotherapy, an increased level of D-dimer is a marker of good prognosis.
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PMID:Incubation of monocytes with adriamycin increases secretion of hepatocyte stimulating factor for fibrinogen biosynthesis. 845 44

A 38-year-old man with a non-Hodgkin's lymphoma of intermediate grade malignancy attained partial remission after three courses of CHOP (cyclophosphamide+hydroxydaunorubicin+vincristine+prednisolone). He was assigned to undergo autologous bone marrow transplantation (ABMT). The conditioning regimen consisted of cyclophosphamide and whole body irradiation. Two weeks later he developed veno-occlusive disease (VOD) of the liver. Doppler sonography confirmed the diagnosis showing a reversal of the blood flow in the portal vein. In addition a large thrombus was present in the inferior caval vein. Protein C level was strongly reduced (28%). Because of clinical deterioration intravenous urokinase was started. The transaminases normalised rapidly and the patient showed a dramatic clinical improvement. There were no major bleeding complications. Repeat Doppler sonography showed a normal antegrade flow in the portal vein. This case suggests that a coagulopathy in the hepatic vascular bed might contribute to the development of VOD and that patients with VOD are at risk for other thrombotic complications. Furthermore it shows that urokinase with platelet support can be given safely and effectively to a patient with VOD and severe thrombocytopenia.
Leukemia 1993 May
PMID:Successful treatment of veno-occlusive disease of the liver with urokinase in a patient with non-Hodgkin's lymphoma. 848 32

We have compared the level of expression of several enhancer/promoters in human lymphoblastoid Namalwa KJM-1 cells when fused to a common reporter gene. A cassette containing the pro-urokinase (pro-UK) coding sequence followed by the rabbit beta-globin and simian virus 40 (SV40) 3' nontranslated region was used for evaluation of the enhancer activity. Cells containing Moloney murine leukemia virus (Mo-MuLV) promoter had an average of 10-20 fold higher expression levels of pro-UK than those containing other promoters, such as SV40 early gene promoter, human cytomegalovirus (hCMV) major immediate-early gene promoter, Rous sarcoma virus (RSV) promoter, and chicken beta-actin gene promoter. The expression level of pro-UK under the control of Mo-MuLV promoter was 2-3 micrograms/10(6) cells/day and was constant for more than 6 months. Furthermore, the production of a high producer clone, obtained by using dhfr gene coamplification, reached 30-40 micrograms/10(6) cells/day. Thus, Mo-MuLV promoter showed the desired characteristics for efficient expression of foreign genes in Namalwa KJM-1 cells.
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PMID:Efficient expression of pro-urokinase by human lymphoblastoid Namalwa KJM-1 cells using moloney retroviral promoter. 892 Jan 7

We demonstrated that urinary trypsin inhibitor (UTI) efficiently inhibits soluble and tumor cell-associated plasmin activity and subsequently inhibits tumor cell invasion and metastasis. The effect of UTI on tumor necrosis factor-alpha (TNF)-induced stimulation of urokinase-type plasminogen activator (uPA) in cultured human umbilical vein endothelial cells (HUVEC) and in the promyeloid leukemia U937 cells was studied. uPA antigen was evaluated in the cell lysate and in the conditioned media by enzyme-linked immunosorbent assay, sodium dodecyl sulfate polyacrylamide gel electrophoresis, and Western blot. TNF can promote the production of uPA in HUVEC and in U937 cells. The PKC inhibitors (H7, calphostin C, and staurosporine) inhibited TNF-induced uPA expression and secretion in a dose-dependent manner. Analysis of the expression of cell surface receptor-bound uPA by flow cytometry using uPA-specific MAb indicates that induction of uPA expression by TNF was inhibited when these cells were incubated with UTI. On the other hand, treatment of the cells with UTI alone failed to alter uPA production. UTI also reduced the secretion of uPA in TNF-treated cells. UTI was as effective as PKC inhibitors in inhibiting uPA expression by TNF. Incubation of the cells with UTI, however, had no effect on the ability of PMA to stimulate cell-associated uPA expression. These data suggest that UTI may influence the PKC-dependent protein kinase pathway in uPA expression. The study on intracellular pathways involved in UTI modulation of uPA will enhance our understanding of the role that UTI plays in uPA-mediated cellular invasion.
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PMID:Urinary trypsin inhibitor efficiently inhibits urokinase production in tumor necrosis factor-stimulated cells. 898 Sep 9


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