Cancer chemotherapy and pharmacology
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Cancer Chemother. Pharmacol. · Jan 1993
Treatment of subcutaneous and intracranial brain tumor xenografts with O6-benzylguanine and 1,3-bis(2-chloroethyl)-1-nitrosourea.
O6-Alkylguanine-DNA alkyltransferase (AT) is a cellular protein that protects cells from the cytotoxic effects of nitrosoureas by repairing alkyl lesions at the O6 position of guanine. We have studied the ability of O6-benzylguanine to deplete AT activity in brain tumor xenografts and thereby increase the sensitivity of these tumors to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). In toxicity studies, pretreatment of athymic mice with O6-benzylguanine increased the toxicity of BCNU significantly. ⋯ These studies suggest that O6-benzylguanine may be a useful adjuvant to nitrosourea therapy in human malignancies that exhibit a range of AT activities and that dose and timing are important variables in achieving therapeutic success. These data also indicate that therapeutic potentiation of BCNU by O6-benzylguanine can be achieved in i.c. tumors. As a result, this approach may be useful in the treatment of neoplasms of the central nervous system.
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Cancer Chemother. Pharmacol. · Jan 1993
Cisplatin-induced neuropathy in mature rats: effects of the melanocortin-derived peptide ORG 2766.
A major side effect of cisplatin treatment is peripheral neuropathy. In the past few years we have provided evidence that the ACTH4-9 analogue ORG 2766 provides protection against this neuropathy in rats and man. In this study we investigated the development of a cisplatin-induced neuropathy and the protective and therapeutic actions of ORG 2766 in mature rats. ⋯ ORG 2766 did not enhance the rate of recovery. In the young adult rats neither ORG 2766 administration nor restricted weight gain significantly influenced either the motor or the sensory nerve conduction velocity. These results validate the animal model of cisplatin-induced neuropathy.