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)

To assess the effects of GM-CSF in patients with myelodysplasia, a total of 101 patients with refractory anemia (RA), RA with ringed sideroblasts (RARS), and RA with an excess of blasts provided that the percentage of blasts in the bone marrow did not exceed 10% (RAEB) were enrolled in the EORTC Leukemia Cooperative Group study 06885. They were randomized to receive two daily subcutaneous injections of rhGM-CSF (mammalian, glycosylated, Sandoz/Schering-Plough) at a daily dose of either 108 micrograms glycoprotein (group I) or 216 micrograms glycoprotein (group II) for 8 weeks. Response was defined as an increase in Hb (greater than 2.5 g%), neutrophil count (more than 100%), or platelet count (more than 100%) without progression of the disease. After exclusion of 19 patients who did not meet the entry criteria, 82 were evaluated. Fifty-four patients (66%) responded (27 of 42 patients in group I and 27 of 40 in group II). Progressive disease was seen in two patients of group I and in four of group II. Two of the latter developed leukemia. All responses were reflected in the granulocytic series. In two patients platelet numbers also increased. Cytogenetic analysis, successfully performed in 43 cases, showed that 14 of 16 patients with normal karyotypes responded, compared with 14 of 27 patients with abnormal karyotypes (p = 0.008). In some cases GM-CSF was reduced in dose or discontinued prematurely due to side effects so that only 35% of all evaluable patients finished 8 weeks of treatment without a change of dose.
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PMID:A randomized phase-I/II multicenter study of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) therapy for patients with myelodysplastic syndromes and a relatively low risk of acute leukemia. EORTC Leukemia Cooperative Group. 158 5

We have analyzed a series of Moloney murine leukemia (M-MuLV) envelope (env) protein fusions to the marker proteins invertase and placental alkaline phosphatase (PLAP), expressed in Psi2 retrovirus packaging cells. The yeast invertase protein, fused at its third amino acid residue to the amino-terminal signal sequence and 17 residues of the mature M-MuLV env protein, retained its enzymatic activity and was secreted from mammalian cells. However, env protein fusions to the C-terminal portion of invertase were inactive. In contrast, some, but not all, env protein fusions at the C-terminal region of PLAP were enzymatically active: PLAP fusions containing long C-terminal portions of env localized to the rough endoplasmic reticulum (RER) and possessed low enzyme activity levels, while fusion constructs containing relatively short portions of the M-MuLV env gene localized to the Golgi and had higher activity levels. Those proteins that localized to the Golgi also were processed, in part, to forms of 67 to 68 kDa, the size of the mature PLAP protein. Since PLAP ordinarily is transferred to a phosphatidyl-inositol glycan tail (PIG-tail) in the Golgi and then transported to the plasma membrane, it appears that Golgi-localized PLAP-env fusions are processed imperfectly. PLAP itself, when expressed in Psi2 cells, accumulated at the plasma membrane and, unlike the PIG-tailed Thy-1 protein, was not incorporated into virus particles. Thus, the reported incorporation of the Thy-1 protein into M-MuLV virions does not appear to be a consequence of its glycoprotein tail.
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PMID:Retroviral envelope protein fusions to secreted and membrane markers. 158 54

The NK and LAK activity of peripheral blood lymphocytes of leukemic patients as well as the susceptibility of their acute myeloid (AML) and lymphoblastic (ALL) leukemia cells to autologous and allogeneic LAKs were examined. In addition, neoplastic cells at diagnosis and at relapse were compared in the same patients for several features, including in vitro susceptibility to LAKs and to the drugs used in the induction phase, expression of MDR phenotype and of adhesion molecules, and differentiation markers. The NK activity of patients' LAK cells on K562 was significantly lower than that of a group of healthy donors whereas no differences were found in LAK activity as evaluated on Daudi cells. Three of 5 AML and 3 of 4 ALL were significantly more susceptible to autologous and allogeneic LAK lysis when blasts obtained at relapse were compared with leukemic cells of the same patients at diagnosis. This different lysability was not associated with in vitro modified sensitivity to drugs used in induction treatment. Moreover, no elevation in the expression of the multidrug-resistance (MDR)-related P170 glycoprotein was noted in relapsing leukemic cells. Even the expression of adhesion molecules and differentiation markers did not correlate with lysability of leukemic cells. These data demonstrate that relapsing leukemic blasts can be significantly lysed by LAK cells and suggest a rationale for adoptive immunotherapy with IL-2 and LAK cells in the treatment of acute leukemic patients.
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PMID:Increased susceptibility to lymphokine activated killer (LAK) lysis of relapsing vs. newly diagnosed acute leukemic cells without changes in drug resistance or in the expression of adhesion molecules. 160 87

The utility of the lipid-associated sialic acid (LASA or LSA) test as a serum marker for malignancy is reviewed. The name LASA or LSA test is confusing because it suggests that only or mainly lipid-bound sialic acid is measured. In reality, glycoprotein-bound sialic acid is determined predominantly. The assay appears to have a particularly high positivity rate in leukemia, Hodgkin's disease, melanoma, sarcoma, advanced ovarian carcinoma and oropharyngeal tumors, suggesting that LASA may serve as a valuable marker in these malignancies. As a consequence of the rise of sialic acid-rich acute-phase proteins, such as alpha 1-acid glycoprotein, in inflammatory diseases the specificity of LASA and therefore its diagnostic accuracy is low. LASA can be useful for monitoring cancer patients during treatment, especially in combination with other tumor markers.
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PMID:The utility of lipid-associated sialic acid (LASA or LSA) as a serum marker for malignancy. A review of the literature. 162 78

A patient with acute myelomegakaryocytic leukemia (AMMgL), which developed from myelodysplastic syndrome (MDS) after chemotherapy against complicated small cell lung cancer, is reported. The patient was a 66 year-old male, who first presented with moderate macrocytic anemia. Bone marrow aspiration showed absolute erythroid hypoplasia and morphological abnormalities were found in erythroid, granuloid and megakaryocytic lineage cells. Iron utilization studies using radioisotope showed ineffective hematopoiesis. He was diagnosed as having MDS (refractory anemia) and treated with prednisolone, fluoxymesterone, and transfusions. After 3 years, small cell lung cancer was found, but he achieved complete remission with chemotherapy. Since then, pancytopenia progressed with myelofibrosis. Abnormal blasts were found in peripheral blood and gradually increased. He finally died from a blastic crisis resulting in gastric bleeding. The blasts were peroxidase negative, platelet peroxidase positive (10%), and glycoprotein II b/III a antibody positive, indicating megakaryoblasts.
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PMID:[Acute myelomegakaryocytic leukemia developed from myelodysplastic syndrome after chemotherapy against complicated small cell lung cancer]. 164 8

The bovine leukaemia virus (BLV) envelope gene encoding extracellular glycoprotein gp51 and transmembrane glycoprotein gp30 was cloned into the HA locus of vaccinia virus (Copenhagen strain), downstream of the vaccinia virus early-late promoter, H6, or a triple promoter element consisting of the promoter for the vaccinia virus H6 gene, the promoter for the cowpox virus A-type inclusion (ATI) gene and the promoter for the vaccinia virus HA gene. Inoculation of rabbits or sheep with the recombinant vaccinia virus coding for gp51 and gp30 or an uncleaved env precursor induced neutralizing antibodies to BLV. These antibodies competed with monoclonal antibodies directed against gp51 epitopes F, G, and H previously shown to be of crucial importance for BLV infection. Seven out of eight sheep vaccinated with the vaccinia recombinants resisted a drastic challenge (1.5 x 10(3) sheep infectious doses) with BLV-infected lymphocytes. These results show that vaccination with BLV env vaccinia recombinants protects sheep against infection with extremely high doses of BLV-infected heterologous lymphocytes.
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PMID:Recombinant vaccinia virus expression of the bovine leukaemia virus envelope gene and protection of immunized sheep against infection. 164 99

The antiviral activity of 6-0-butanoylcastanospermine (MDL 28,574) [50% inhibitory concentration (IC50: 1.1 microM)] in JM cells infected with a recent isolate of HIV-1 (GB8), was compared with other inhibitors of glycoprotein-processing enzymes. N-butyldeoxynojirimycin (BuDNJ), deoxynojirimycin (DNJ), castanospermine (CAST) or the reverse transcriptase inhibitor 2'3'-dideoxycytidine (ddC) had activities of 56, 560, 29 and 0.1 microM, respectively. MDL 28,574 was at least 50 times more active than BuDNJ and less active but better tolerated in cell culture than ddC, two compounds currently undergoing clinical trials. The CAST derivative showed good protection in H9 cells infected with HIV-1 (RF; IIIB; U455), and HIV-2 (ROD), although the potency was less than that seen in the JM/GB8 system. HIV-1 glycoproteins, gp160 and gp120, synthesized in H9 cells chronically infected with HIV-1 (RF) and treated with MDL 28,574, were characterized by an increase in relative molecular weight of approximately 7-8000 kD. The ratio of gp120 to gp160 was markedly reduced in treated cells and provided further evidence that cleavage of the gp160 precursor molecule is a major consequence of the inhibition of glycoprotein processing. The intracellular target for MDL 28,574 was verified as alpha-glucosidase-I of the processing enzymes by the analysis of high-glucose glycopeptides recovered from treated mouse cells. This activity correlated with the antiviral effect observed against the growth of a mouse retrovirus, Moloney murine leukemia virus (MOLV), in mouse cells.
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PMID:6-0-butanoylcastanospermine (MDL 28,574) inhibits glycoprotein processing and the growth of HIVs. 165 79

After elimination of the virus fraction non-associated with bovine leukemia virus (free) glycoprotein gp-51 antigen has been preparatively isolated from the supernatant of the FLK cell culture. For this purpose ultrafiltration through PM-30 membrane, thrice-repeated isoelectric focusing with different (pH 3.0-10.0, pH 4.0-6.0) ampholine intervals and affinity chromatography with ConA-sepharose are used. The SDS-polyacrylamide gel electrophoresis has determined it to be a homogeneous protein with molecular weight 51,000 daltons. The results of the enzyme-linked immunosorbent assay, immunoelectrophoresis and agar-gel immunodiffusion test confirm the specific activity of isolated gp-51 antigen. The gp-51 antigen may be used for identification of antibodies in the blood serum of leukemia virus of infected cattle and for monoclonal screening of antibodies.
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PMID:[Glycoprotein (gp-51) antigen not associated with the bovine leukemia virus in FLK culture supernatant liquid]. 165 7

Feline leukemia virus is a naturally occurring, contagiously transmitted and oncogenic immunosuppressive retrovirus of cats. The effects of FeLV are paradoxical, causing cytoproliferative and cytosuppressive disease (eg, lymphoma and myeloproliferative disorders vs immunodeficiency and myelosuppressive disorders). In the first few weeks after virus exposure, interactions between FeLV and hemolymphatic system cells determine whether the virus or the cat will dominate in the host/virus relationship--persistent viremia and progressive infection or self limiting, regressive infection will develop. The outcome of these early host/virus interactions is revealed in the diagnostic assays for FeLV antigenemia and viremia. The latter, in turn, predict the outcome of FeLV infection in cats. Known host resistance factors include age and immune system functional status. Known virus virulence factors are magnitude of exposure and virus genotype. Molecular analysis of FeLV strains indicated that natural virus isolates exist as mixtures of closely related virus genotypes and that minor genetic variations among FeLV strains can impart major differences in pathogenicity. The genetic coding regions responsible for cell targeting and specific disease inducing capacity (eg, thymic lymphoma, acute immunosuppression, or aplastic anemia) have been mapped to the virus surface glycoprotein and/or long terminal repeat regions for several FeLV strains. Infection by specific FeLV strains leads to either malignant transformation or cytopathic deletion of specific lymphocyte and hemopoietic cell population, changes that prefigure the onset of clinical illness. Another notable feature of the biology of FeLV is that many cats are able to effectively contain and terminate viral replication, an important example of host immunologic control of a retrovirus infection and a process that can be selectively enhanced by vaccination. Thus, FeLV infection serves as a natural model of the multifaceted pathogenesis of retroviruses and as a paradigm for immunoprophylaxis against an immunosuppressive leukemogenic retrovirus.
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PMID:Feline leukemia virus infection and diseases. 166 70

Tests were performed to determine whether live mammalian cells producing env gene glycoproteins and main structural protein p24 of bovine leukaemia virus (BLV), heterologous to bovine species, could serve as an immunogen in cattle to prevent induction of bovine leukaemia. Ovine virus-non-producing clonal cells NP-2 were used as the immunogen. The NP-2 cells synthesized only the env gene products--glycoprotein gp51 and gp30 and main structural protein p24 of BLV. The NP-2 cells, inoculated into rats, induced an antibody response directed against envelope glycoproteins of BLV. The antibodies neutralized the infectivity of BLV as determined by the VSV/BLV pseudotype neutralization test. Similar results were obtained by vaccination of cattle with these cells. A dose of less than or equal to 2 x 10(6) live cells inoculated subcutaneously induced an antibody response in cattle, while a high dose of killed cells was ineffective. The antibodies in cattle were directed against env products of BLV. A group of 92 cows was vaccinated and followed up for 4 years. The antibody levels fluctuated slightly during the 4-year observation period, generally decreasing with time, but revaccination always increased the antibody titre. No transfer of seropositivity was observed to seronegative animals which were kept in contact with vaccinated ones. In a separate experiment a group of young heifers, after repeated vaccination, were challenged with a high dose of infectious virus and/or virus-producing cells. The response to BLV infection was followed by syncytial induction assay after co-cultivation of white blood cells with indicator cells CC81.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Protective vaccination against bovine leukaemia virus infection by means of cell-derived vaccine. 166 47


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