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)

In vivo or in vitro immunity to murine leukemia virus (MuLV)-induced leukemia cells which do not effectively produce virus, has been difficult to demonstrate. Because immunizations with allogeneic murine leukemia cells have been used to confer syngeneic tumor immunity to virus- producing cells, we attempted to generate lymphocytes, cytotoxic to syngeneic nonproducer leukemia cells, by stimulating normal murine spleen cells with allogeneic nonproducer leukemia cells in mixed tumor lymphocyte culture (MTLC) reactions in vitro. Secondary allogeneic MTLC of normal C57BL/6 or DBA/2 spleen cells effectively produced syngeneic tumor-specific cytotoxic lymphocytes. Target cells lysed in lymphocyte- mediated cytolysis (LMC) assays, included both Friend and Rauscher virus- induced syngeneic murine leukemia cells and chemically-induced hematopoietic tumor cells. Syngeneic tumor cells were lysed regardless of whether they produced infectious MuLV or expressed viral antigens gp-71, p-30, or p-12 at the cell surface. Syngeneic normal cells (thymus, lymph node, or Concanavalin A-stimulated spleen cells) used as targets in LMC assays were uneffected by lymphocytes harvested from secondary allogeneic MTLC. Several other in vitro culture treatments including secondary syngeneic MTLC and repetitive mixed lymphocyte culture stimulations were incapable of generating tumor-specific cytotoxic lymphocytes. Based upon these results, we propose that secondary MTLC stimulation of normal spleen cells with allogeneic nonproducer leukemia cells selects for the proliferation of two subpopulations of antigen-specific cytotoxic lymphocytes. The population capable of effecting syngeneic tumor cell lysis is directed against tumor-associated cell surface antigens which may be distinct from viral structural proteins or glycoproteins. The growth of these tumor-specific cytotoxic lymphocytes may be enhanced by a soluble allogeneic effect factor produced by the proliferation of the second subpopulation of lymphocytes generated in repetitive allogeneic MTLC, namely those lymphocytes with specificities directed against differing histocompatibility antigens.
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PMID:In vitro generation of tumor-specific cytotoxic lymphocytes. Secondary allogeneic mixed tumor lymphocyte culture of normal murine spleen cells. 6 3

5-Aza-2'-deoxycytidine administered at a daily dose of 1.5 mg/kg increased the life-span of P388 leukemia-bearing BALB/c X DBA/2 F1 mice by 5 times and that of second generation lymphoma-bearing AKR mice by 2.5 times. Higher doses (total dose, 20 mg/kg) led to favorable results when administered in two portions on Days 4 and 5 after the s.c. inoculation of leukemic cells. The same total dose given on 5 consecutive days was toxic. The lethal dose that killed 50% of the animals was 190 mg/kg. The drug was also effective in L1210 leukemia. 5-Aza-2'-deoxycytidine inhibited the phosphorylation of 2'-deoxycytidine in the acid-soluble pool of cells from leukemic AKR mice as well as its incorporation into DNA. In vitro the inhibition of the uptake of 2'-deoxycytidine into cells from leukemic mice by 5-aza-2-deoxycytidine had a competitive character (Ki, 8 X 10(-5) M). Although 5-aza-2'-deoxy[4-14C]cytidine of low-specific activity was not detected in DNA isolated from the lives of leukemic mice, the same tritium-labeled drug of high-specific radioactivity was selectively localized in the nuclei of leukemic cells as revealed by autoradiography. The incorporation of [3H]-5-aza-2'-deoxycytidine into DNA of cells from leukemic mice was confirmed by the chromatographic separation of DNA on a column of kieselguhr coated with methylated albumin.
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PMID:Incorporation of a potent antileukemic agent, 5-aza-2'-deoxycytidine, into DNA of cells from leukemic mice. 7 Nov 99

Previous studies have demonstrated that the Rauscher virus induces a biphasic erythroleukemia in DBA mice, and the regression of the disease is connected with the appearance of antibody-dependent cellular cytotoxicity. In the present work, attempts were made to reveal the mechanism leading to the lethal exacerbation of the leukemia. In the sera of leukemic mice soluble tumor-specific antigen could be demonstrated in the stages of early progression and regression but not in the stage of exacerbation. The antigen was present in form of immune complexes with free antibodies in excess. The emergence of a new population of leukemia cells has been observed during the stage of regression. On the surface of these cells the antigen receptor sites were masked by sialic acid which resulted in the loss of immunosensitivity and immunogenicity.
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PMID:Immune response to Rauscher virus-induced leukemia in DBA mice. II. Correlation between antigenic expression and pathogenesis. 7 84

A spontaneous T cell lymphoma of DBA/2 (H-2-d) mice, SL2, was found to react with anti H-2 typing sera raised against certain foreign haplotypes as well as with anti H-2d sera. The cytotoxic anti-SL2 activity of the anti-foreign H-2 sera was detected in a newly developed microradioassay, not however, in a conventional 51Cr release test. Upon culture in vitro the reactivity of the tumor cells with the anti H-2 sera decreased. The anomalous cytotoxic anti-tumor activity of the anti-foreign H-2 sera appeared to be distinct from anti-murine leukemia virus activity, since it was not removed by absorption with either Friend of AKR leukemia virus. Partial absorption was observed with normal lymphoid cells carrying the respective foreign H-2 antigens, but not with cells of unrelated H-2 haplotypes. In each serum tested, the anti-tumor activity could also be absorbed with syngeneic H-2d lymphoid cells. These results show that the anomalous anti-tumor reactivity of certain anti H-2 typing sera, in particular of sera raised in recipients differing in H-2 from the tumor host strains, is not due to the presence of foreign (derepressed) H-2 molecules on the tumor cells. The differences observed between the tumor cells and normal cells seem to be due to unexpected antibodies in the sera reacting with public H-2 specificities which are better exposed on the tumor cells than on normal cells.
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PMID:Characterization of antigens on murine tumor cells reacting with alloantisera against foreign H-2 specificities: analysis by absorption with purified murine leukemia virus and normal lymphoid cells of different H-2 haplotypes. 8 74

A cytotoxic antibody for L1210 leukemia cells was found in the (C57BL/6 x DBA/2)F1 (BDF1) mice immunized with L1210 leukemia cells infected with ts mutant of HVJ (HVJ-pi) and challenged several times with uninfected L1210 leukemia cells. These immune mice fell into two categories; high and low responders regarding the titer of cytotoxic antibody produced. The antigen defined by this cytotoxic antibody was present on leukemia cells originating in DBA/2 mice but not on leukemia induced by passage-A Gross virus or spontaneous mammary tumors. This serological cross-reactivity among L1210, P388, and L5178Y leukemia cells has been substantially confirmed by the observation of cross protection against challenge with DBA/2 leukemia cells in immune BDF1 mice. These findings strongly suggested the presence of a common DBA/2 leukemia-associated antigen different from known cell-surface antigens of murine leukemia. The results obtained in the present work also demonstrated the great efficacy of non-cytopathic, viable HVJ-pi-injected tumor cells as an immunogen for inducing tumor immunity.
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PMID:Common leukemia-associated antigen of DBA/2 mouse leukemia detected by tumor rejection and complement-dependent cytotoxicity assays. 9 22

Infection with the Friend murine leukemia virus complex (F-MuLV) suppressed humoral antibody synthesis in vivo and lymphocyte mitogenesis in vitro. Both these effects of F-MuLV were under host genetic control. In vitro suppression of lymphocyte mitogenesis was regulated by a single autosomal gene called Fv-3 that is dominant for susceptibility. Genetic analyses, with the use of the susceptible DBA/2 and resistant B10.D2/n parents, their F1, intercross, and backcross progeny, indicated that a single autosomal gene dominant for susceptibility regulated the in vivo susceptibility to immunosuppression by F-MuLV. Individual [(DBA/2xB10.D2)F1xB10.D2] mice were typed both for susceptibility to F-MuLV-induced suppression of lymphocyte mitogenesis in vitro (an Fv-3 function) and susceptibility to immunosuppression by F-MuLV in vivo. Such an analysis indicated that the same mice that were susceptible or resistant to immunosuppression in vivo were susceptible or resistant to suppression of lymphocyte mitogenesis in vitro. Spearman's rank analysis of the data also indicated that the in vivo and in vitro immunosuppressive effects of F-MuLV were correlated with and not independent of each other. Thus Fv-3, which regulates the effect of F-MuLV on lymphocytes in vitro, also appears to regulate the effect of F-MuLV on antibody-forming cells in vivo.
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PMID:Mechanism of genetic resistance to Friend virus leukemia in mice. V. Relevance of Fv-3 gene in the regulation of in vivo immunosuppression. 10 Jun 4

In vitro L1210 (V) cell lines contained abundant intracytoplasmic A-particles, numerous C-type particles, a small number of B-type particles, and occasional intracisternal A-particles. The intracytoplasmic A-particles were incorporated into both spiked (B-type) and smooth-surfaced (C-type) particles formed at the budding site. Both B-and C-type particles also developed by gradual accululation of neucleooid material. The particles, particularly the C-type, exhibited a wide range of densities. The cells showed strong surface immunofluoresence for both murine mammary tumor virus and Gross murine leukemia virus antigens and variable degrees of cytoplasmic immunoflurescence for the protein antigens (p1 to p6) of Rauscher leukemia virus. The cells, the culture supernatant, and the purified virus each gave positive reactions with murine mammary tumor virus and murine leukemia virus antisera by immunodiffusion. The viral particles failed to infect C57BL, C57BL/6 X DBA/2F1 (hereafter called BD2F1), BALB/c, Af,and RIIIf mice. Howver, the cells were highly tumorigenic in BD1F-1 mice, moderately tumorigenic in BALB/c mice, but not tumorigenic in C57BL, Af, and RIIIf mice.
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PMID:Identification of the virions in the in vitro L1210(V) leukemia cell lines by morphological, virological, and immunological techniques. 16 89

Upon analyses of 59 inbred strains, F-1 hybrids, and congenic-resistant mouse strains, the strain distribution pattern of the stimulation of perippheral mouse lymphocytes by phytohemagglutinin was established using a micromethod. The family of DBA mice were the lowest responders of phytohemagglutinin, whereas the C57 family responded best. Strain PL/J exhibited the best response. The response of lymphocytes to the lectin is governed by more than two but less than five major genes of unknown linkage. No direct association to the H-2 histocompatibility complex was found, although an indirect influence of this locus could not be excluded. All high-leukemia strains are good responders to phytohemagglutinin. None of the low-responder-group strains exhibit spontaneous leukemia. No correlation of the response of lymphocytes to the expression of the type C RNA genome could be established. Cell suspensions from animals exhibiting clinical signs of leukemia responded only weakly or not all to the lectin.
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PMID:Heritability of the phytohemagglutinin responsiveness of lymphocytes and its relationship to leukemogenesis. 16 91

The distribution of the normal differentiation antigen Thy 1 and the mammary tumor virus (MTV)-induced antigens or antigen complexes MLm and MLr were studied in mouse mammary gland cells, mammary tumor cells, and other cell types, by use of ascites leukemia cells of the GR mouse strain as target cells in the cytotoxicity test. The Thy 1.2 antigen was detected by an AKR antiserum to C3Hf thymocytes. MLm was shown by a homologous C57BL antiserum to GRSL2 leukemia (absorbed in vivo in GR mice); MLr was detected by a rabbit heterologous antiserum (absorbed in vivo in C57BL or GR mice and in vitro with BALB/c milk) prepared against Tween 80- and ether-treated purified B particles. Sera from Sprague-Dawley rats bearing murine leukemia virus (MuLV)-producing syngeneic tumors were not cytotoxic or only slightly cytotoxic for GR leukemias transplanted in vivo, which indicated that MuLV-induced antigens were absent or present in very low quantity in such leukemias. The MLr and MLn antigens or antigen complexes were possibly identical to the mammary leukemia (ML) antigen, since they could be detected not only on GR but also on DBA/2 leukemia cells and since their distribution was exactly the same as that of MTV. Both the MLr and MLm antigens were present in purified B particles, and antigenic activity were present in purified B particles, and antigenic activity was enhanced by destruction of the purified virus particles. The antigens were about eightfold enriched in a preparation of B-particle envelopes, as shown by quantitative cytotoxicity absorption (CYTA) tests. Purified nucleoid fractions of B particles were only lightly positive for the antigen, probably due to envelope contamination. One dominant gene was responsible for the expression of MLr, as shown by CYTA tests with mammary glands of individual animals of segregating crosses between the GR strain with high mammary cancer incidence and strains with low incidence. This gene was closely linked with or was possibly identical to 1) the gene for cytoplasmic MTV gs antigen expression as seen by fixed cell immunofluorescence, and 2) the gene causing mammary tumors in the GR mouse strain.
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PMID:Immunologic, virologic, and genetic aspects of mammary tumor virus-induced cell-surface antigens: presence of these antigens and the Thy 1.2 antigen on murine mammary gland and tumor cells. 16 86

Titration of N- and B-tropic murine leukemia viruses on sensitive and resistant cell lines has been studied by direct XC plaque assay and infective center assay. The titration of cloned B-tropic virus by infective center assay on BALB/3T3 (Fv-1b/b) and NIH/3T3 (Fv-1n/n) cells gave one-hit patterns, with 100-fold less infected NIH/3T3 cells than BALB/3T3 cells. The titration of B-tropic virus on DBA/2 cells (Fv-1n/n) was also a one-hit. The titration of a one-hit curve, and there were about 100-fold less infected BALB/3T3 cells than NIH/3T3 cells. Comparable results were obtained by titrating the cloned N-tropic virus on congenic SIM (Fv-1n/n) and SIM.R (Fv-1b/b) cells or the Gross N-tropic virus on BALB/3T3 cells. Therefore, our data indicate that the multiple-hit phenomenon described previously may not be an essential part of the Fv-1 gene restriction.
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PMID:Effect of the Fv-1 locus on the titration of murine leukemia viruses. 17 59


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