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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Leukemic cells from all human chronic granulocytic leukemia (CGL) and some acute myelomonocytic leukemia (AMML) donors are lysed by rabbit antisera to a purified glycoprotein of Friend murine leukemia virus (FLV gp71) in a microcytotoxicity assay. These antisera are not cytotoxic to cells from patients with acute myelocytic leukemia (AML), acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), or to peripheral blood lymphocytes from normal donors. A goat antiserum to gradient purified FLV in addition to reacting with cells from CGL and AMML donors also reacted with cells from AML patients and some ALL donors. However, this antiserum failed to react with cells from CLL patients. Peripheral blood and bone marrow leukocytes prepared from leukemic patients in clinical remission failed to react with antisera to FLV and FLV gp71. Absorption experiments demonstrated that the antigen on CGL cells which is reacting with the antiserum to FLV gp71 is also present on normal human platelets and neutrophils. Similar absorption studies showed that the antigen on AML cells detected by the FLV antiserum is not present on normal leukocytes and platelets and appears to be related to the major internal p30 antigens of mammalian RNA tumor viruses. Another antigenic relationship between oncornaviruses and membrane antigens of human leukemia cells was shown by the ability of FLV antigens to absorb the cytotoxic reactivity of nonhuman primate antisera detecting human leukemia-associated antigens. FLV and FLV gp71 antigens were able to absorb all cytotoxic activity of monkey and chimpanzee antisera to human myeloid leukemia antigens when these antisera were tested with CGL cells. These two approaches to an analysis of cross-reactivity indicate that the antigenic determinant(s) detected by the cytotoxic reactions of the FLV gp71 antiserum with human CGL cells is different from the determinant on FLV gp71 which is responsible for the inhibition of the reactivity of simian antisera with CGL cells. Since the goat and rabbit antisera to FLV and FLV gp71 are able to distinguish AML from CGL cells by direct cytotoxicity testing and absorption, they may be valuable reagents for the serological diagnosis of myeloid leukemia. In addition, since peripheral blood cells from AML and CGL patients in clinical remission were seronegative, the antisera may be valuable as management aids. The data in this report indicates that whatever the mechanism of leukemogenesis is in man, cells from CGL and AML patients possess certain membrane antigens which cross-react with FLV structural components such as p30 and gp71.
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PMID:Relationships between membrane antigens of human leukemic cells and oncogenic RNA virus structural components. 5 69

Particles possessing a density of 1.16 g/ml and encapsulating a 70S RNA and a RNA-instructed DNA polymerase (reverse transcriptase) have been prepared from the spleen of a patient with chronic lymphocytic leukemia. These particles have been converted to cores with a density of 1.26 g/ml and containing the enzyme-RNA complex, in complete analogy to the known RNA tumor viruses of avian and murine origin. The reverse transcriptase was purified from the cores by column chromatography to a stage showing a single major protein band of 70,000 daltons in a gel electrophoresis. The enzyme was capable of transcribing heteropolymeric RNA into DNA complements as demonstrated by specific back hybridization to template RNA. The leukemic spleen would appear to represent an important source of this enzyme, as well as other potentially important leukemia-specific reagents.
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PMID:Purification of RNA-instructed DNA polymerase from human leukemic spleens. 5 34

Friend leukemia cells growing in suspension culture are thought to represent a population of primitive erythroid cells which have undergone malignant transformation. We have found that when growing in vivo or in plasma clots in vitro, these suspension culture cells can exhibit morphologic and enzymatic properties which are characteristic of primitive granulocytic cells. The microenvironment in which the tumor cells grow plays a major role in determining the direction of differentiation of these leukemia cells. Hence it appears likely that the Friend cell is in fact a neoplastic pluripotent hematopoietic stem cell.
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PMID:Granulocyte differentiation by Friend leukemia cells. 5 19

By employing the 125IUdR release cytotoxicity assay, we have been able to measure the primary and secondary cell-mediated cytotoxic response of C57BL/6 mice to FBL-3 cells, a syngeneic Friend virus-induced leukemia. It was found that the secondary cell-mediated cytotoxic response occurred more rapidly after challenge (within 3 days) than the primary response, and the levels of reactivity were considerably higher. As in the primary response, the secondary cytotoxic reactivity of spleen cells was T cell dependent, being eliminated by pretreatment with anti-theta antibody plus complement. However, the secondary reactivity of pertioneal exudate (PE) cells was not entirely T-cell dependent. The specificity of the secondary cytotoxic response was analyzed by primary or secondary immunization with various tumor cells and by testing of cytotoxic lymphocytes against a variety of target cells. When spleen cells were used for testing, only tumor cells induced by Friend, Moloney, or Rauscher (FMR) leukemia viruses could produce secondary cell-mediated cytotoxic responses against FBL-3 cells. This correlated well with the specificity observed in the in vivo tumor transplantation protection studies. Similarly, spleen cells immune to FBL-3 had appreciable cytotoxicity against tumor cells induced by FMR viruses. The FBL-3 immune mice also gave significant protection against the challenge of FMR leukemias. When PE cells were used for testing, they gave higher levels of cytotoxicity against tumor cells induced by FMR viruses, but also gave less, but appreciable, cytotoxicity against non-FMR tumors. The latter reactivity might be related to the antigens induced by the murine endogenous type C viruses.
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PMID:Cell-mediated immunity to Friend virus-induced leukemia. III. Characteristics of secondary cell-mediated cytotoxic response. 5 88

Immunoregulatory alpha-globulin (IRA) derived from normal human plasma decreased cytotoxic reactivity as measured by an in vitro 5-iodo-2'-deoxyridine release assay of immune mouse lymphocytes against the syngeneic Friend virus-induced leukemia, FBL-3. This inhibitory effect depended on the dose of IRA used and was not due to the cytotoxic effects of IRA on the effector cells or target tumor cells. We also found elevated levels of serum alpha-gloubins in FBL-3 tumor-bearing mice as compared to normal mice. These data and the demonstration of decreased specific cytotoxic reactivity in FBL-3 tumor-bearing mice suggest that IRA functions in the suppression of the host's immune response against tumors.
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PMID:In vitro inhibition of cell-mediated cytotoxicity against syngeneic Friend virus-induced leukemia by immunoregulatory alpha globulin. 5 38

Virions of Moloney murine leukemia virus can synthesize two classes of DNA molecules complementary to their 70S RNA. One class consists of molecules about 200 nucleotides long, which are of limited sequence complexity; these molecules are formed preferentially if the dNTP concentration during the reaction is low. The second class consists of very heterogeneous DNA molecules with weight-average size of about 1,000 nucleotides containing at least 70% of the viral RNA sequences in approximately equal concentration. The longest of these molecules can be 5,000 nucleotides long. This second class of DNA is formed in large amounts only in reactions containing dNTP concentrations of 0.2 mM or higher. In such reactions after 24 h of incubation, at least 35% of the input RNA is represented in DNA copies. The ability to make long, representative DNA transcripts of tumor virus RNA provides a source of excellent probes for molecular hybridization.
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PMID:Synthesis of long, representative DNA copies of the murine RNA tumor virus genome. 5 41

Autogenous immune sera from several strains of mice have been examined for type-, group-, or interspecies-specific reactivities against leukemia virus envelope antigens and virus-induced cell surface proteins. The natural antibody of these test sera react with gp69/71, gp43, and p15 structural components on murine leukemia viruses including AKR, Friend, Rauscher, Moloney, and xenotropic BALB:virus-2. Furthermore, comparable radioimmune titration curves are obtained when these viruses are used in radioimmune precipitation assays. Competition experiments, however, suggest that natural immune sera are predominantly type specific and only weakly cross-react with the Rauscher or Friend virus. Natural immune sera react with the virion envelope but not with the virus-induced cell surface antigen. With respect to the biological activity of autogenous immune sera, there appears to be an inconsistency between the spectrum of virus-precipitating antibody and virus-neutralizing antibody. Although normal mouse serum readily neutralizes xenotropic viruses (BALB:virus-2), only weak neutralization of the ecotropic viruses can be achieved in vitro. Although there is a lack of direct evidence to indicate that autogenous immunity to murine leukemia virus is involved in the control of virus-mediated neoplasia, several empirical correlations point in this direction.
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PMID:Autogenous immunity to endogenous RNA tumor virus: humoral immune response to virus envelope antigens. 5 22

Cell-mediated immune reactions appear to play an important role in resistance against growth of leukemia cells in mice. Possible mechanisms for in vivo protection in two tumor systems are discussed. These tumor models, which are a Friend leukemia virus-induced transplantable tumor, FBL-3, and primary murine sarcoma virus (MSV) -induced tumors, are strongly antigenic; under some conditions, tumors regress completely. In mice with regressing FBL-3 tumors, cell-mediated cytotoxicity was measured by release of [125I]iododeoxyuridine. The response was biphasic, with an initial peak at 10 days and a 2nd peak after 30 days. A boost in reactivity could be elicited by later challenge with tumor cells. All of the reactivity was dependent on T-cells, being eliminated by treatment with anti-theta plus complement. The specificity of the reactions was not completely defined, but it was consistent with Friend type-specific antigen plus broader, common antigens. In mice with regressing MSV tumors, strong cell-mediated cytotoxicity, measured mainly by release of 51Cr, was seen against RBL-5, a Rauscher virus-induced leukemia. A single peak of response occurred at about 14 days after virus inoculation. Upon later challenge with RBL-5 cells, a vigorous and rapid secondary response was elicited, mainly in the region of tumor challenge. This cytotoxic reactivity and in vivo resistance to leukemia.lso was completely dependent on T-cells. In addition, macrophage-mediated inhibition of leukemia cell growth in vitro was seen in this system at the time of peak tumor development. The 51Cr release cytotoxicity was specific and directed primarily against an antigen, MEV-SA1, associated with mouse endogenous C-type viruses. The macrophage-induced growth inhibition appeared to be nonspecific. In both the FBL-3 and MSV tumor systems, protection against tumor growth could be adoptively transferred by immune lymphoid cells. In addition to induction of cell-mediated immunity by tumor cell or virus inoculation, cell-mediated cytotoxic reactivity was found to occur naturally in most young mice. This natural killer activity was quite distinct from the experimentally elicited reactions, being mediated by N-cells, a subpopulation of lymphoid cells with no clearly identifiable cell surface markers. The natural cytotoxicity was also directed against antigenic specificities different from those recognized by the MSV-immune cells. The central issue in all of these studies has been to determine the relationships between the in vitro-detected cell-mediated reactivity and in vivo resistance to leukemia.
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PMID:Cell-mediated immunity to leukemia virus- and tumor-associated antigens in mice. 5 23

Cats represent an unusually valuable model for studying the role of the immune response to leukemia, lymphoma, and other mesodermal neoplasms. The agents that cause spontaneous feline leukemias, lymphomas, and fibrosarcomas, the feline leukemia and sarcoma viruses, are well characterized. A specific tumor cell membrane antigen, designated the feline oncornavirus-associated cell membrane antigen (FOCMA) has also been described. Feline leukemia and feline sarcoma viruses are antigenically indistinguishable, and FOCMA is common for both. Both laboratory-induced and spontaneous feline leukemias, lymphomas, and fibrosarcomas are available for study. A clear correlation has been shown between the resistance of cats to development of lethal tumors following inoculation of feline sarcoma virus and the presence of high humoral antibody titers to FOCMA. The geometric mean antibody titer to FOCMA for cats that resisted growth of fibrosarcomas was more than 20-fold higher than the mean for cats that succumbed to lethally progressing tumors. Cats with induced or spontaneous leukemia or lymphoma also have either no detectable FOCMA antibody or very low levels. Conversely, some cats resist development of leukemia or lymphoma following natural exposure to feline leukemia virus in leukemia cluster households, and these cats have high FOCMA antibody titers. These results support the concept of a natural immunosurveillance mechanism against leukemia or lymphoma development in an outbred mammalian species.
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PMID:Immune response to leukemia virus and tumor-associated antigens in cats. 5 24

1-beta-D-Arabinofuranosylcytosine (cytarabine; ara-C) and 5-azacytidine (5-azaCR), cytosine nucleoside antimetabolites with different mechanisms of action, are both effective in the treatment of human leukemia, and the clinical use of these two agents in combination has been suggested. We have studied the therapeutic effect in L1210 leukemic mice of single i.p. doses of ara-C and 5-azaCR in combination. Therapeutic effects observed depended markedly on the sequence and time interval between the doses of each agent. Antagonism was observed when both agents were administered simultaneously. The optimal therapeutic effect was observed when 5-azaCR was administered after ara-C at a time when tumor DNA synthesis had maximally recovered after the ara-C dose. The dose-interval effect and correlation with recovery of DNA synthesis capacity were also observed in studies in vitro in which the survival of L1210 cells in culture was examined. ara-C was shown to inhibit the incorporation of [4-14C]-5-azaCR-derived radioactivity into DNA of L1210 cells in culture, and the therapeutic effects observed are interpreted in terms of these latter results and the mechanisms of action of the two agents.
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PMID:Combination chemotherapy of L1210 leukemia with 1-beta-D-arabinofuranosylcytosine and 5-azacytidine. 5 29


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