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Biomedical subjects

A Fefer

Publications and source records attributed to A Fefer.

At least 145 records · Page 8Linked to original sources

Effect of dimethylmyleran on cell-mediated immunity to a tumor allograft.

C57BL/6 mice (H-2b) were inoculated on day 0 with killed Moloney lymphoma cells (LSTRA) of BALB/c origin (H-2d), and their spleen cells were tested for reactivity against LSTRA by the 51Cr-release cytotoxicity assay. Cytotoxic reactivity of cells from ice not treated with drug was maximal by day 6 and disappeared by day 10. Cells from mice given dimethylmyleran (DDM) (12 or 16 mg/kg) on day -1 showed higher levels of cytotoxicity, whereas DMM administered on day +1 had little effect. The effect of DMM on the secondary response was tested and compared with that of cyclophosphamide (CY), 180 mg/kg. Cytotoxicity of cells from mice immunized on days 0 and 10 was maximal on day 15 and then declined. CY administered on day 11 prevented the development of any cytotoxicity and, when given on day 14 in the presence of a detectably strong secondary cytotoxic response, abolished the established response. In contrast, DMM given on day 11 delayed the onset and moderately decreased the peaks of secondary reactivity but had no effect when administered on day 14. These results showed that DMM enhanced a primary response, interfered somewhat with the development of a secondary response, and had no effect on an established secondary cell-mediated response to a tumor allograft. DMM thus was one of the rare agents with antitumor activity and little immunosuppressive action.

Animals

Suppression of secondary cellular immunity to a tumor allograft by cyclophosphamide and 1,3-bis(2-chloroethyl)-1-nitrosourea.

C57BL/6 mice (H-2b) were immunized with lethally x-irradiated Moloney virus-induced lymphoma cells of BALB/c origin (H-2d) on Days 0 and 10 and received rug on Days 11 and 14. Their spleen cells were then tested for reactivity against Moloney virus-induced lymphoma of BALB/c origin by the 51Cr-release cytotoxicity assay. In non-drug-treated mice the secondary cytotoxic response was maximal on Days 14 to 15, declined rapidley, and recurred after Day 21. The cytotoxic effector cells were shown to be theta-bearing T-lymphocytes. Cyclophosphamide (CY), 180 mg/kg, given on Day 11, totally prevented the development of a cytotoxic response and when given on Day 14 abolished the response already established. CY, 48 mg/kg, as well as 1,3-bis(2-chloroethyl)-1-nitrosourea 33 mg/kg, were almost as suppressive. Immune mice given CY on Day 14 and reimmunized on Day 36 exhibited a normal tertiary response. Mice similarly immunized on Days 1 and 10 and given drugs on Day 14 were challenged on Day 15 with up to 3.5 x 10-8 viable Moloney virus-induced lymphoma cells of BALB/c origin. Despite H-2 incompatibility, all nonimmune control mice developed ascites and died, whereas all mice immunized but not given drug failed to develop ascites. By contrast, 17 of 34 immunized mice given CY, 180 mg/kg, and 7 of 34 given 1,3-bis(2-chloroethyl)-1-nitrosourea developed ascites. The ascites eventually regressed. THE RESULTS SHOW THAT CY and 1,3-bis(2-chloroethyl)-1-nitrosourea can suppress a secondary cellular immune response as measured by the T-cell-mediated 51Cr-release cytotoxicity assay in vitro and by viable tumor challenge in vivo.

Animals

Syngeneic adoptive immunotherapy and chemoimmunotherapy of a Friend leukemia: requirement for T cells.

The aim of the study was to determine which cell mediates adoptive immunotherapy and chemoimmunotherapy of a syngeneic transplantable Friend virus-induced leukemia (FBL-3). An adoptive immunotherapy model was developed in which adult C57BL/6 mice given a lethal dose (10(4)) of FBL-3 on day 0 were saved by treatment on day 1 with C57BL/6 spleen cells or peritoneal exudate cells (PEC) immune to FBL-3. Cells passed through a nylon wool column to remove B cells and macrophages or treated with carbonyl iron to remove phagocytic cells remained effective, whereas cells treated with anti-theta serum and complement were far less effective. For adoptive chemoimmunotherapy, mice inoculated with 10(7) FBL-3 were treated 5 days later with cyclophosphamide (CY) plus immune spleen cells. CY, with or without non-immune cells, prolonged survival but all mice died with leukemia, whereas mice given CY plus immune cells survived tumor-free. As an adjunct to CY, immune cells passed through nylon wool or treated with carbonyl iron remained quite effective whereas cells treated with anti-theta serum and complement were far less effective. Thus, immune thymus-derived lymphocytes were required for the adoptive immunotherapy of an early leukemia or chemoimmunotherapy of a disseminated leukemia.

Animals

Peroxidase-H2O2-halide system: Cytotoxic effect on mammalian tumor cells.

Myeloperoxidase, H2O2, and a halide constitute a potent antimicrobial system. A cytotoxic effect of this system on a line of mouse ascitic lymphoma cells (LSTRA) is demonstrated here using four different assay systems: 51Cr release, trypan blue exclusion, inhibition of glucose C-1 oxidation, and loss of oncogenicity for mice. Deletion of each component of the system, preheating the peroxidase, or addition of azide, cyanide, or catalase abolished the cytotoxicity. Myeloperoxidase was effective with either chloride or iodide as the halide, while lastoperoxidase was effective with iodide but not chloride. The iodinated thyroid hormones, triiodothyronine and thyroxine, could substitute for the halide, and H2O2 could be replaced by a peroxide-generating enzyme system such as glucose and glucose oxidase or by H2O2 producing bacteria such as pneumococci or streptococci. The possibility is raised that the peroxidases of inflammatory cells and certain biologic fluids may affect tumor initiation or growth in vivo.

Animals