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)

BALB/c mice receiving allogeneic C3H/He spleen cells via portal venous (p.v.) route or a single administration of cyclophosphamide (Cy) were capable of rejecting allogeneic X5563 tumor cells (C3H/He origin). In contrast, the combined treatment of p.v. inoculation with C3H/He cells and Cy administration abrogated the capability of rejecting allogeneic X5563 tumor cells. The dose of Cy and interval between p.v. presensitization and Cy injection needed to be more than 1.5 mg Cy/mouse and less than 2 days, respectively. Such abrogation of alloreactivity was alloantigen-specific, since p.v. inoculation of C3H/He cells followed by Cy injection resulted in selective inhibition of rejecting allogeneic C3H/He tumor cells (X5563 plasmacytoma) without suppressing the capability of rejecting allogeneic C57BL/6 tumor cells (EL4 leukemia). Most important, the induction of alloantigen-specific unreactivity by p.v. presensitization plus Cy injection contrasted with the failure of intravenous or subcutaneous presensitization plus Cy injection to induce tolerance that permits the growth of allogeneic tumor cells inoculated. This was substantiated by the finding that p.v. presensitization with C3H/He cells prior to Cy injection eliminated anti-C3H/He cytotoxic T lymphocyte (CTL) and delayed-type hypersensitivity (DTH) potentials under conditions in which appreciable CTL and DTH responses are induced in mice inoculated via the i.v. route before Cy injection. These results demonstrate that p.v. inoculation of allogeneic cells followed by a single administration of Cy results in more efficient elimination of antialloantigen CTL and DTH reactivities, leading to the abrogation of potential to reject the allogenic tumor graft.
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PMID:Tolerance induction of alloreactivity by portal venous inoculation with allogeneic cells followed by the injection of cyclophosphamide. I. Specific suppression of alloreactive cytotoxic and delayed-type hypersensitivity responses as well as allograft rejection. 349 52

Multivalent hybrid antibodies with dual specificity were prepared by cross-linking with protein A two antibodies of different specificity, one against ricin toxin and the other against the H-2 antigens of murine leukemia EL4 cells. This bifunctional antibody specifically attached to EL4 cells was able to capture ricin toxin (RcA2) molecules with an affinity 20 times higher than that of the galactose-containing glycoproteins of the cell surface (nonspecific binding). The hybrid-bound RcA2 gained access into the target cell cytoplasm by endocytosis and blocked [3H]thymidine incorporation as efficiently as free RcA2 does on nontreated EL4 cells (3.3 X 10(-11) M). These results indicate that multivalent hybrid antibody, easy to prepare in purified form and endowed with high affinity for both target cell and ricin toxin, may be utilized efficiently for the specific delivery of toxins to target cells.
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PMID:Binding and cytotoxic effect of ricin toxin on multivalent hybrid antibody-coated target cells. 349 87

Delivery of the lethal hit signal to target cells (TC) by cytolytic T lymphocyte (CTL) has traditionally been considered strictly dependent upon the presence of external Ca2+ [( Ca2+]ext) in the medium, but neither the role of Ca2+ nor its site of action (effector or target) have been known. We have observed that in different CTL/TC systems the requirement for [Ca2+]ext varies, depending on the target. Some TC, like leukemia L1210, are strictly dependent on [Ca2+]ext for lysis while others, like EL4 (and P815), are not. It is therefore suggested that, where required, [Ca2+]ext exerts its effect(s) on the TC and not the CTL. In support of this conclusion are experiments showing that effector cells cytolytic to certain TC in the absence of [Ca2+]ext, require [Ca2+]ext when used themselves as TC of other effectors. Verapamil, a Ca2+-channel blocker, inhibits the lysis of L1210 but not of EL4 cells, suggesting involvement of Ca2+ flux into L1210 target cells and, if at all involved, Ca2+ mobilization from internal stores in EL4. The different lytic susceptibility of the two TC to the Ca2+ ionophore A23187, in the presence and absence of [Ca2+]ext, correlated with their responses to CTL. It suggests Ca2+ influx into both types of TC in the presence of [Ca2+]ext and its release from internal stores in the lysis of EL4 but not L1210 in the absence of [Ca2+]ext. In view of these results indicating that the target is the site of Ca2+ action, we propose that CTL induce a Ca2+-regulated activation of the TC leading to its lysis.
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PMID:T-Lymphocyte-mediated cytolysis as an excitatory process of the target. I. Evidence that the target cell may be the site of Ca2+ action. 392 77

Two BALB radiation leukemias are strongly rejected by hybrids of BALB with certain other mouse strains, although BALB mice themselves exhibit no detectable resistance whatever. Hybrids immunized with progressively increased inocula are resistant to 200 x 10(6) or more leukemia cells; their serum is cytotoxic for the leukemia cells in vitro and protects BALB mice against challenge with these BALB leukemias. The antigenic system thus identified has been named X.1. In (BALB x B6) hybrids the major determinant of resistance was shown to be a B6 gene in the K region of H-2. This is likely to be the Rgv-1 (Resistance to gross virus) locus of Lilly, which may thus be identified in this case as an Ir (Immune response) allele conferring ability to respond to X.1 antigen on MuLV and leukemia cells, and so responsible for production of X.1 antibody and the rejection of X.1(+) leukemia cells by hybrid mice. Immunoelectron microscopy with X.1 antiserum (from immunized hybrids) shows labeling both on the cell surface and on virions produced by the leukemia cells. It is not known whether X.1 comprises only one or more than one antigen. Three radiation-induced BALB leukemias, one A strain radiation-induced leukemia, and 15/15 AKR primary spontaneous leukemias were typed X.1(+) by the cytotoxicity test. Several other leukemias, including one induced by passage A Gross virus and one long-transplanted AKR ascites leukemia carried in (B6 x AKR)F(1) hybrids, were X.1(-). Normal mice of strains with a high incidence of leukemia and one other strain (129) express X.1 antigen, but evidently in amounts too small for certain detection in vitro; by the method of absorption in vivo, however, these strains could be typed X.1(+) and other strains X.1(-). We ascribe the X.1 antigen system tentatively to a sub-type of MuLV that is not passage A Gross virus and is probably not the dominant sub-type in strains with a high incidence of leukemia. After repeated passage in hybrids, one of the BALB leukemias became relatively resistant to rejection by the hybrid, partially lost its sensitivity to X.1 antiserum in vitro, and in electron micrographs was seen to produce fewer virions. The serum of untreated (BALB x B6) hybrids often contains cytotoxic antibody against leukemia cells, some of it probably anti-X.1. But another commonly occurring antibody, which is cytotoxic for C57BL leukemia EL4, appears to belong to another (undefined) system.
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PMID:Leukemia-associated transplantation antigens related to murine leukemia virus. The X.1 system: immune response controlled by a locus linked to H-2. 472 15

Peritoneal exudate cells (PEC), obtained after the rejection of EL4 leukemia by BALB/c mice, are much more effective in the specific in vitro destruction of (51)Cr-labeled EL4 cells than are spleen, thymus, lymph node, or peripheral blood lymphocytes. The presence of a large number of effector cells at the site of graft rejection is reflected in the potent cytolytic activity seen in vitro. Effector cells temporarily lose cytolytic reactivity when treated with trypsin but regain reactivity with time. This recovery occurs in normal as well as in immune serum. The destructive reactivity of PEC is increased when macrophages are removed. The remaining population of nonadherent PEC is composed primarily of small- to medium-sized lymphocytes. Complex tissue culture media are not needed, but there is a definite requirement for serum. The required serum component is heat stable, nondialyzable, and is not consumed during the reaction. The use of an ascites allograft system made these observations possible and permitted the isolation of those host cells intimately associated with rejection.
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PMID:Rejection of ascites tumor allografts. I. Isolation, characterization, and in vitro reactivity of peritoneal lymphoid effector cells from BALB-c mice immune to EL4 leukosis. 502 38

Lymphocytes in peritoneal exudate from BALB/(c) mice immunized against ascites leukemia EL4 are uniquely efficient at destroying (51)chromiumlabeled EL4 cells in vitro. The lytic process depends upon the number of lymphocyte-tumor cell interactions. Efector lymphocytes are not inactivated as a result of lethal contact but can interact repeatedly with tumor cells.
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PMID:Tumor immunity in vitro: destruction of a mouse ascites tumor through a cycling pathway. 504 43

Murine leukemia EL4 cells were modified by supplementation of culture media with fatty acids for 24 h. A plasma membrane-enriched fraction was prepared from substituted and normal cells. Analyses were performed to determine fatty acyl composition, phospholipid headgroup composition and cholesterol content. The two major membrane phospholipids, phosphatidylethanolamine (PE) and phosphatidylcholine (PC) were isolated by thin-layer chromatography and ESR measurements were done on liposomes prepared from these lipids as well as on the intact plasma membrane preparations. Slight perturbations in overall plasma membrane lipid composition were observed when EL4 cells were supplemented with a single exogenous fatty acid. This may be consistent with the idea that the incorporation of exogenous fatty acid induces compensatory changes in membrane lipid composition. On the other hand, we observed no significant difference in two ESR motional parameters between the unsubstituted control and various fatty acid-substituted plasma membranes. ESR measurements carried out on PE and PC liposomes derived from 17:0- and 18:2c-substituted membranes also failed to detect major differences between these liposomes and those made from normal EL4 phospholipids. In the case of liposomes prepared from 18:2t,-substituted membranes, the order parameter was significantly changed from the normal. However, the change was in opposite directions in PE and PC, perhaps accounting for the fact that no change parameter is seen in intact 18:2t-substituted plasma membrane. Measurements of order parameter (S) in mixed lipid vesicles showed that at up to 50 mol% mixture of a synthetic PC with plasma membrane PC, the value of S was only marginally different from that of the plasma membrane PC vesicles. We interpret these data as an indication that the two ESR parameters used are not sufficiently sensitive to detect changes due to modifications of the acyl chain composition of a complex biological membrane.
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PMID:The relationship between plasma membrane lipid composition and physical-chemical properties. III. Detailed physical and biochemical analysis of fatty acid-substituted EL4 plasma membranes. 628 97

The adenosine deaminase (ADA) inhibitor erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA), at low concentrations (less than 10 microM), enhances the inhibitory activity of adenosine against lymphocyte-mediated cytolysis (LMC) without itself being inhibitory. At higher concentrations, EHNA alone is inhibitory to LMC with an IC50 of 160 microM. This inhibition is reversible upon washout, appears to affect an early stage of the lytic process, and does not appear to involve changes in basal levels of cyclic AMP (cAMP), ribonucleoside 5'-triphosphate pool sizes, S-adenosylhomocysteine levels, or protein carboxymethylation. EHNA does enhance the cAMP response of cytolytic lymphocytes (CL) to activators of adenylate cyclase such as prostaglandin E1. EHNA inhibits lymphocyte high-affinity cAMP phosphodiesterase at immunosuppressive levels, exhibiting hyperbolic mixed-type inhibition (Ki = 83 microM, alpha = 0.47, beta = 0.18). Whereas inhibition of intralymphocytic ADA is complete at low concentrations (less than 25 microM) of EHNA, inhibition of LMC and intralymphocytic cAMP phosphodiesterase increases linearly with EHNA concentration to at least 200 microM. The presence of 200 microM EHNA during the centrifugation of mixtures of CL and EL4 leukemia target cells leads to increased CL cAMP levels. 2'-Deoxycoformycin, a more potent ADA inhibitor than EHNA, is not inhibitory to LMC and shows none of these cAMP-related effects. These results suggest that CL-target cell contact stimulates adenylate cyclase in the CL and that EHNA inhibits LMC due to its enhancement of this target cell-stimulated elevation of cAMP.
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PMID:Inhibition of lymphocyte-mediated cytolysis and cyclic AMP phosphodiesterase by erythro-9-(2-hydroxy-3-nonyl)adenine. 629 34

The immunogenic properties of one (or few) selected antigen(s) encoded by the mouse major histocompatibility complex was studied using the C57BL/6(B6) mouse strain and its descendant B6.C-H-2bm1(bm1) mutant. These strains differ in a point mutation in the H-2K region. We compared the immunogenic and antigenic expression of the mutated antigen on different bm1 tissues by testing the vulnerability of these tissues to graft rejection response in B6 recipients. Previous results demonstrated that B6 and bm1 mice do not reject reciprocal thyroid transplants, despite the acute rejection of reciprocal skin grafts. Thyroid grafts were rejected, however, after presensitizing the recipients with skin graft syngeneic with the thyroid, but not after sensitization with spleen cells. In the present work we induced tumors in bm1 mice by treating them with a chemical carcinogen (3-methylcholanthrene). We found that two out of four tumors demonstrated strict strain specificity and were rejected by all mouse strains (including the B6 recipients) except by their strain of origin. All tumors were found to be sensitive to in vitro lysis by B6 anti-bm1 effector cells. HZ1-A and HZ1-B tumor cells were rejected by B6 recipient mice but could not immunize B6 mice against a subsequent bm1 thyroid graft. When testing the immunogenicity of B6 originated EL4 leukemia cells (which are fatal to B6 mice), we found that the tumor cells were rejected by bm1 recipients, but, unlike B6 skin grafts, were incapable of inducing the rejection of a subsequent B6 thyroid transplant. The results demonstrated that an H-2K molecule may exhibit different immunological properties when expressed on cells of different tissues. The different expression of the mutated antigen on different cell types, its ability to trigger T cells but not B cells responses and the potential involvement of the tissue specific differentiation molecules in the graft rejection response are discussed.
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PMID:Immunogenicity of the mutated H-2Kbm1 antigen(s). Test of thyroid graft rejection between B6.C-H-2bm1 and C57BL/6 mice following reciprocal immunization with normal versus malignant cells. 636 78

The antitumor activity of 7-N-(p-hydroxyphenyl)mitomycin C (M-83) against 7 kinds of ascitic tumors and 4 kinds of solid tumors was compared with that of mitomycin C (MMC). M-83 showed more potent activities than MMC against ascites sarcoma 180, fibrosarcoma Meth 1, sarcoma Meth A, melanoma B-16, leukemia P388 and lymphoma EL4, by a single intraperitoneal injection. Furthermore, M-83 gave markedly higher chemotherapeutic ratio than MMC in these tumor systems. M-83 was also markedly effective against solid tumors of sarcoma 180, Meth 1, Meth A and Lewis lung carcinoma, by a single intravenous injection. M-83 gave lower myelo-suppression than MMC at the doses which gave almost equal inhibition on the tumor growth of solid Meth 1. M-83 and MMC significantly inhibited the growth of HeLa S3 cells. Cell growth was observed at 24 hours after addition of 3 X 10(-3) mM of drugs, but no growth was shown thereafter. M-83 inhibited more strongly the incorporation of the radioactive precursor into DNA than that into RNA or protein at the concentration of 3 X 10(-3) mM.
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PMID:Comparative antitumor activities of 7-N-(p-hydroxyphenyl)mitomycin C (M-83) and mitomycin C. 640 71


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