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)

RADA-1 cells (H-2a), a murine leukemia cell line maintained by serial transfer in histocompatible recipients expressing thymus-leukemia (TL) 1, 2, 3 antigenic determinants, resisted the cytotoxic effects of guinea pig complement (GPC) and TL antiserum. The cells expressed a lower density of TL antigens than did ASL-1 cells, another TL(+) leukemia cell line expressing the same determinants and susceptible to complement (C)-mediated lysis. Stable somatic cell hybrids of RADA-1 cells and LM(TK)- cells (H2k), a TL(minus) thymidine kinase-deficient mutant of mouse L cells, were selected in hypoxanthine-aminopterin-thymidine medium. The hybrid cells expressed the H-2 antigens of both parents and shared a hybrid karyotype. They formed TL 1, 2, 3 antigens as determined by immunofluorescence, mixed hemagglutination methods, the direct isolation of TL antigens from Nonidet P40 extracts of the cells, and the capacity of the cells to reduce by absorption the known titers of TL antiserum. These hybrid cells lost the capacity to resist lysis by TL antiserum and GPC. They were susceptible to the cytotoxic effects of TL 1, 2, 3; TL 2; OR TL 1, 3 antiserum and GPC, even though the density of TL antigens associated with the cells was approximately 25% of their resistant RADA-1 parental cells. These results indicated that the mechanism of resistance to C-mediated lysis was genetically separable from the expression of TL antigens by the cells and that the susceptibility of the cells to the cytotoxic effects of antiserum was related only in part to the density of TL antigens expressed by the cells.
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PMID:Complement sensitivity of somatic hybrids of a complement-resistant murine leukemia cell line. 5 Oct 86

A somatic hybrid of ASL-1 leukemia cells [H-2a, thymus leukemia (TL)1,2,3, Thy-1b] and LM(TK)-cells [H-2-k, TL(-), Thy-1 (-), thymidine kinase deficient] was formed with the aid of inactivated Sendai virus. The selection of hybrid cell clones was facilitated by the inability of ASL-1 cells to grow in vitro and of LM(TK)-cells to survive in hypoxanthine/amethopterin/thymidine medium. The H-2 antigens of both parental cells were formed in approximately equivalent amounts by the hybrid cells, and they possessed a hybrid karyotype. As determined by five independent experimental procedures (antibody and complement-mediated cytotoxicity tests, the reduction of specific antibody activity of antiserum of known titer, immunofluorescent tests, mixed hemagglutination tests, and their direct isolation), TL antigens but not Thy-1 antigens were formed by the hybrid cells. TL antigens of the hybrids failed to undergo modulation under conditions leading to the modulation of TL antigens of parental ASL-1 cells. Modulation was attempted with TL 1,3, TL 2, or TL 1,2,3 antisera of high titer. thybrid cells were incubated for up to 30 hr in medium with TL antisera. Both direct and indirect immune methods were attempted. These results indicate that cellular mechanisms controlling the expression of TL antigens may be distinguished from the capacity of the cells to undergo modulation.
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PMID:Somatic hybrid of thymus leukemia (. 16 80

The quantity of thymus-leukemia (TL) antigens expressed by murine leukemia cells is significantly greater than that expressed by somatic hybrids of such cells. Based upon the results of 125I-lactoperoxidase labeling and antibody absorption procedures, and corrected for size differences between the two cell types, the quantity of TL antigens expressed by RADA-1 cells, a radiation-induced murine leukemia cell line of strain A/J mice, is approximately 5.0 times greater than that of somatic hybrids of RADA-1 and LM(TK)- cells. LM(TK)- cells are a thymidine kinase-deficient TL(-) mouse fibroblast cell line. The quantity of TL antigens expressed is related only in part to their susceptibility to lysis by TL antibodies and guinea pig complement (GPC). RADA-1 cells resist lysis. The quantity of TL antigens expressed by RADA-1 cells is analogous to that formed by nonneoplastic thymocytes obtained from F1 hybrids of two strains of TL(+) and TL(-) mice; cells from both strains are sensitive to TL antiserum and GPC. ASL-1 cells, a spontaneously occurring leukemia cell line of A/J mice, express TL antigens in significantly higher quantities than any of the cell types examined. Exposed to TL antisera, the quantity of TL antigens of ASL-1 cells, but not that of hybrid cells, gradually diminishes. ASL-1 cells convert over a 6-h period of exposure to antibody and guinea pig complement (GPC) resistance; hybrid cells remain sensitive. However, ASL-1 cells converted to TL antibody and GPC resistance continue for a time to express TL antigens in quantities similar to that of sensitive F1 thymocytes and resistant RADA-1 cells. RADA-1 X LM(TK)- hybrid cells, which are sensitive to TL antibodies and GPC, express the lowest quantities of TL antigens of any of the cell types examined. It is likely that differences in the quantities of TL antigens expressed by different cell lines reflect genetic mechanisms controlling TL antigen expression. The failure of TL antisera to affect the quantities of TL antigens expressed by hybrid cells is taken as an indication that genetic controls governing antigen expression may be distinguished from those involved in regulating responsiveness to specific antiserum.
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PMID:Murine leukemia cell hybrids: the quantity of TL antigens expressed by parental and hybrid cells fails to correlate with their sensitivity to TL antibody and complement. 75 Jul 64

The effect of specific antisera on the metabolic rates of thymus-leukemia (TL), H-2a, and tumor-associated antigens of ASL-1 and RADA-1 cells, two murine leukemia cell lines, were determined. The metabolic half-life of each antigen was distinct from the others examined. The half-life of TL antigens was 18 hr; in cells exposed to TL antiserum, it changed to 9 hr. In RADA-1 cells, the half-life of TL antigens was 16 hr; in the presence of TL antiserum it became 4 hr. The half-lives of H-2a antigens and the tumor-associated antigen were unaffected by specific antiserum. Somatic hybrids of ASL-1 or RADA-1 cells were formed with LM(TK)-cells, a thymidine kinase deficient mutant of mouse L cells. Hybrid cells formed TL antigens, but unlike their parental cells their half-life of expression, approximately 30 hr, was unaffected by TL antiserum. Hybrid cells failed to undergo antigenic modulation under conditions more stringent than required to stimulate the modulation of ASL-1 or RADA-1 cells. The hybrids formed the tumor-associated antigen of their murine leukemia parental cells; however, the metabolic rate of the tumor antigen in hybrid cells was defferent than the metabolic rate of the analogous antigen in parental cells. Hybrid cells formed H-2 antigens of both parental sources, and possessed a hybrid karyotype. The half-life of H-2 antigens, approximately 26 hr, was the same both in parental and hybrid cells. H-2a antiserum had no detectable effect upon the metabolism of TL antigens in hybrid or parental cells; nor did TL antiserum have an effect upon the metabolism of H-2a antigens.
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PMID:Independent control of the expression of several membrane-associated antigens of murine leukemia cells: metabolism and response to specific antiserum. 103 Aug 6

The env and gag genes from feline leukaemia virus were expressed in a thymidine kinase-negative feline herpes-virus and a baculovirus. Cats were vaccinated with various combinations of these recombinant viruses and 100% protection against feline leukaemia virus challenge was achieved using an immunization schedule which utilized both env and gag products delivered at both a mucosal and systemic site.
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PMID:The use of feline herpesvirus and baculovirus as vaccine vectors for the gag and env genes of feline leukaemia virus. 132 Dec 14

Tumor cells infected with a retrovirus vector (VIK) containing the herpes simplex virus thymidine kinase (HSV-TK) gene can be selectively killed by treatment with nucleoside analogues, such as ganciclovir. To mediate delivery of the HSV-TK gene to "recipient" tumor cells, "donor" C6 rat glioma cells infected with the VIK vector (C6VIK) were superinfected with wild type Moloney murine leukemia virus (WT Mo-MLV). These modified donor cells (C6VIKWT) produced both wild type retrovirus and the VIK vector. In culture, C6VIKWT cells were 300-fold more sensitive to the toxicity of ganciclovir than were C6VIK cells, suggesting that the presence of wild type retrovirus contributed to the toxicity. Co-culture of C6VIKWT cells with the C6 subline, C6BAG, sensitized the latter to ganciclovir treatment. Nude mice inoculated subcutaneously with a mixture of C6VIKWT and C6BAG cells showed regression of subsequent tumors when treated with ganciclovir. The observations show that tumor cells modified in culture by infection with a retrovirus bearing the HSV-TK gene and wild type retrovirus are not only sensitive to ganciclovir, but can transfer this sensitivity to neighboring "naive" tumor cells in culture and in vivo.
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PMID:Gene therapy of malignant brain tumors: a rat glioma line bearing the herpes simplex virus type 1-thymidine kinase gene and wild type retrovirus kills other tumor cells. 133 91

A possible approach to control of bovine lymphoproliferative disease caused by bovine leukaemia virus (BLV) may be the development of an "antiviral information immunity" based on the effect of anti-sense RNA (asRNA). A numbers of constructs were obtained, under control of various promotors (herpesvirus thymidine kinase, T-antigen SV40 promoter), carrying as DNA against gene X, the expression product of which is a transactivator of viral transcription from the BLV LTR promotor. As a model system for the analysis of antiviral activity of constructs developed, cloned continuous cell lines of BLV-producing FLK cells were used. The level of BLV expression in cells transfected with the constructs was determined by various parameters. Differences were detected in different clones obtained from non-transfected cells, as well as variation between transfected clones, as measured by reverse transcriptase, competitive radio-immunoassay for BLV p24, the viral particle count on agar membrane, and the tumorigenicity for nude mice. The differences in inhibition of expression of BLV genes and their products may be explained in terms of the site of integration of asDNA and the number of integrated copies.
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PMID:An investigation of the effect of antisense RNA gene on bovine leukaemia virus reproduction in cell culture. 133 48

Human cells salvage pyrimidine deoxyribonucleosides via 5'-phosphorylation which is also the route of activation of many chemotherapeutically used nucleoside analogs. Key enzymes in this metabolism are the cytosolic thymidine kinase (TK1), the mitochondrial thymidine kinase (TK2) and the cytosolic deoxycytidine kinase (dCK). These enzymes are expressed differently in different tissues and cell cycle phases, and they display overlapping substrate specificities. Thymidine is phosphorylated by both thymidine kinases, and deoxycytidine is phosphorylated by both dCK and TK2. The enzymes also phosphorylate nucleoside analogs with very different efficiencies. Here we present specific radiochemical assays for the three kinase activities utilizing analogs as substrates that are by more than 90 percent phosphorylated solely by one of the kinases; i.e. 3'-azido-2',3'-dideoxythymidine (AZT) as substrate for TK1, 1-beta-D-arabinofuranosylthymidine (AraT) for TK2 and 2-chlorodeoxyadenosine (CdA) for dCK. We determined the fraction of the total deoxycytidine and thymidine phosphorylating activity that was provided by each of the three enzymes in different human cells and tissues, such as resting and proliferating lymphocytes, lymphocytic cells of leukemia patients (chronic lymphocytic, chronic myeloic and hairy cell leukemia), muscle, brain and gastrointestinal tissue. The detailed knowledge of the pyrimidine deoxyribonucleoside kinase activities and substrate specificities are of importance for studies on chemotherapeutically active nucleoside analogs, and the assays and data presented here should be valuable tools in that research.
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PMID:Selective assays for thymidine kinase 1 and 2 and deoxycytidine kinase and their activities in extracts from human cells and tissues. 135 86

Resistance to methotrexate (MTX) is a well established clinical problem and strategies to circumvent this would obviously be beneficial. The human leukemia cell line, CCRF-CEM, was grown in folinic acid to study MTX resistance-reflecting more in vivo conditions. A 15.8-fold resistant subline, CEM/MTX, was evolved by stepwise increases in MTX exposure. The MTX resistant cell line exhibited both increased dihydrofolate reductase (DHFR) activity due to gene amplification as well as impaired MTX uptake. An additional mechanism of resistance to MTX was a 2-fold increase in thymidine kinase (TK). As a result of this increased TK activity, the CEM/MTX cells were collaterally sensitive to the nucleoside analogue, azidothymidine (AZT). CEM cells resistant to MTX possess properties that can be exploited by AZT and these studies may have clinical implications.
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PMID:Collateral sensitivity to azidothymidine in methotrexate resistant human leukemia cells. 138 29

To determine the effect of different promoters on the expression of an altered dihydrofolate reductase (DHFR) gene conferring methotrexate (MTX) resistance in different cell types, double-copy retroviral vectors were constructed carrying a murine mutant DHFR under the control of five different promoters, i.e., human adenosine deaminase (ADA), simian virus 40 (SV40), thymidine kinase (TK), human beta-actin, and cytomegalovirus (CMV). Their expression was compared in NIH-3T3 cells, three human leukemia cell lines, and mouse bone marrow. The variant DHFR is readily expressed from these various promoters in retroviral vectors at a selectable level. In 3T3 cells, the DHFR constructs containing the SV40 promoter conferred the highest levels of resistance to MTX. In K562 and Raji cells, the construct with the TK promoter produced the highest level of resistance. However granulocyte-macrophage colony-forming unit (CFU-GM) colonies from mouse marrow were more resistant to MTX when infected with vectors containing the SV40 promoter and ADA promoter as compared to the other promoter constructs. These studies show that mouse fibroblast cell lines such as NIH-3T3 do not predict the effectiveness of retroviral-mediated gene transfer for marrow progenitor cells, and that the activity of retroviral vector-encoded promoters vary in an unpredictable manner from cell type to cell type. Possible implications for basic gene transfer studies and clinical applications are discussed.
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PMID:Comparison of the expression of a mutant dihydrofolate reductase under control of different internal promoters in retroviral vectors. 152 11


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