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  • 1
    ISSN: 1432-0851
    Keywords: Vaccine ; Immunostimulator ; L1210 leukemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We have investigated the ability of a novel immunopotentiator, 7-thia-8-oxoguanosine (7T8OG) to increase the efficacy of a weakly immunogenic murine L1210 leukemia vaccine. The vaccine was prepared by irradiating L1210 leukemia cells in a cesium source with a total of 6000-R dose. DBA/2 mice were treated with 150 mg/kg 7T8OG and/or with vaccine consisting of 107 irradiated cells. In combination therapy, mice first received the vaccine and then were injected with 75 mg/kg 7T8OG 2 h and 4 h after vaccination. One week after the last treatment all mice were inoculated with 104 live leukemia cells intraperitoneally. Control, untreated mice (n = 66) injected with 104 live leukemia cells had a mean survival time ± standard error of 10.5±0.2 days. Treating mice (n = 66) with one, two or three doses of 7T8OG administered i.p. 1 week apart did not increase survival (mean survival time = 10.7 days). Mice immunized with one, two or three doses of vaccine had 14.5±1.1, 45.4±6.2 and 68.3±10.6 days mean survival, respectively. 7T8OG-stimulated vaccination increased the survival dramatically. The best survival was noted when the mice were treated with 2× (vaccine + 7T8OG). Immunization of mice (n = 30) with this treatment regimen increased the mean survival to 156±10.0 days. Over 90% of mice that were treated this way had a cumulative survival time greater than 160 days. In contrast, only 12% of the mice immunized twice with the leukemia vaccine alone survived over 160 days. These results suggest a rationale for the use of this immuno-potentiator with various vaccines for a more effective immunization.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Clinical & experimental metastasis 9 (1991), S. 429-439 
    ISSN: 1573-7276
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have recently reported that a synthetic nucleoside, 7-thia-8-oxoguanosine (7T8OG) is a potent activator of a number of effectors which are involved in anti-tumor immune responses. 7T8OG was found to induce interferon (IFN) production, to activate asialo-GM1 positive (AGM1 +) killer cells, and to enhance specific antibody responses. In the present study, we investigated the effect of 7T8OG on growth of the murine pulmonary B16 melanoma and on formation of metastases. C57BL/6 mice were injected i.p. with 50–150 mg/kg 7T8OG before or after i.v. inoculation of B16 melanoma tumor cells, and 17–19 days after tumor inoculation, the number of metastases in the lungs were counted. 7T8OG given systemically in a single or a divided dose 24 h prior to the challenge of tumor cells reduced the number of lung tumor metastases by 89–99% which is highly significant as compared to untreated control (P〈0.001). Occasional extra pulmonary tumor growth in the thoracic cavity and neck lymph node was also completely inhibited. The reduction in the number of tumor nodules was dose dependent. A single dose of 150 mg/kg of 7T8OG was also effective in inhibiting the growth of 3–5 day old metastatic tumors. The cytotoxic activity of killer cells inducedin vivo by 7T8OG was completely abolished byin vitro treatment of cells with antiAGM1 antibody plus complement. Administration of anti-AGM1 antibody following the 7T8OG treatment completely abrogated the anti-tumor effect of 7T8OG, resulting in a massive increase in the number of tumor foci in the lungs. Administration of carageenan or silica followed by injection of 7T8OG caused a significant increase (P〈0.01) in the number of pulmonary tumor nodules compared to treatment with 7T8OG only. These findings indicate that activated macrophages or perhaps their cytokine (tumor necrosis factor) also contribute to the host tumor defense by 7T8OG.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Neurochemical research 19 (1994), S. 1131-1137 
    ISSN: 1573-6903
    Keywords: Alzheimer's disease ; glucose-6-phosphate dehydrogenase ; glutathione ; superoxide dismutase ; catalase ; malondialdehyde ; lipid peroxidation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Alzheimer's disease may arise from or produce oxidative damage in the brain. To assess the responses of the Alzheimer's brain to possible oxidative challenges, we assayed for glutathione, glucose-6-phosphate dehydrogenase, catalase and superoxide dismutase in twelve regions of Alzheimer's disease and aged control brains. In addition, we determined levels of malondialdehyde to evaluate lipid peroxidation in these brain regions. Most brain regions showed evidence of a response to an oxidative challenge, but the cellular response to this challenge differed among brain regions. These data suggest that the entire Alzheimer's brain may be subject to an oxidative challenge, but that some brain areas may be more vulnerable than others to the consequent neural damage that characterizes the disease.
    Type of Medium: Electronic Resource
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