Cancer research
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4-Methyl-5-amino-1-formylisoquinoline thiosemicarbazone (MAIQ-1) was studied to determine its potential for clinical trail as a second-generation antineoplastic agent of the alpha-(N)-heterocyclic carboxaldehyde thiosemicarbazone class. MAIQ-1 was shown to be among the most potent known inhibitors of the major target for the expression of antineoplastic activity by this class of agents, the enzyme ribonucleoside diphosphate reductase, requiring only 0.06 micronM for 50% inhibition. This potency at the enzymatic level was consistent with its antineoplastic activity against the murine neoplasms Sarcoma 180, Leukemia L1210, Leukemia P388, and the B16 melanoma. ⋯ In vivo metabolism of MAIQ-1 in mice, studied with [3'-14C]MAIQ-1 showed that relatively slow excretion of this agent occurred, since the cumulative urinary excretion of radioactivity was only 35% in 48 HR. About 51% of excreted urinary radioactivity was present in chromatograms in an area corresponding to the iron chelate of MAIQ-1, and only a minor quantity of material migrating like acetylated MAIQ-1 was present in urine, a finding consistent with enzymatic data with liver homogenates. The results indicate that MAIQ-1 has the antineoplastic activity, enzyme inhibitory potency, and relative resistance to metabolic inactivation required of an agent of this class for clinical trials.
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Brain-associated antigens have been detected on human and mouse thymocytes. Also, murine neuroblasts and brain cells have common antigens. In this study we compared the reactivity of rabbit anti-human brain (HB) serum with neoplastic neuroblasts and normal and neoplastic lymphoid cells. ⋯ We conclude that human neuroblastoma cells possess cell-surface antigens that are present on HB. These antigens appear to be species specific and are not present on normal or malignant thymic cells. Conversely, thymus-associated antigens are not expressed on neuroblasts.