By F. S. Philips (auth.), Franco M. Muggia, Charles W. Young, Stephen K. Carter (eds.)
F. M. MUGGIA while confronted with the inadequacies of present melanoma therapy, we like to examine what the longer term may possibly carry. generally, we take with no consideration the earlier, who prefer learn into completely new parts. although, the power improvement of fertile soil could yield marvelous rewards in the event you decide to construct at the wisdom of the past--hence, this symposium on anthracycline antibiotics. even supposing the anthracycline antibiotics symbolize a lot of the current and way forward for melanoma therapy, their genuine use c stretches again slightly 20 years to the pioneering efforts of Aurelio Di Marco, who characterised the antitumor homes of daunomycin and adriamycin. * The medical software of those compounds heralded a decade of pleasure between oncologists facing pediatric tumors, breast melanoma, leukemias, and lymphomas, and opened new wish for sufferers troubled with sar comas and a number of different tumors that have been deemed - sistant to chemotherapy. those successes have been tempered with the belief that the antitumor impression of anthracyclines will be accomplished now and then purely on the very excessive expense of risking cardiac decompensation and, nearly constantly, with the incidence of alopecia and different acute toxicities. This checklist of previous achievements and difficulties has slowly given method to a gift more and more illuminated through our skill to change the distressing toxicities of those brokers. certain scientific reports supplemented by means of inventive laboratory versions have progressively elucidated mechanisms and probability components im plicated within the cardiomyopathy.
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Extra resources for Anthracycline Antibiotics in Cancer Therapy: Proceedings of the International Symposium on Anthracycline Antibiotics in Cancer Therapy, New York, New York, 16–18 September 1981
C Purified microsomes prepared according to reference no. 21. 34 In ~ vitro short-term tests, adriamycin induces frameshift mutants in Salmonella typhimurium TA98 (see below) and malignant transformation in mouse M2 fibroblasts (see above). t mit 0 c h0 n d ria 1 c e 11 f r act ion tot he bacterial assay (Table 5) and induction of microsomal enzyme activity by 2,5-diphenyloxazole in M2 cells (Table 6) decreases these biological effects. Conversely, inhibition of microsomal enzyme activity in M2 cells by a-naphthoflavone or SKF-525A increases the yield of drug-induced transfor mations (Table 6).
Administration, the agent was at least as active at inducing mammary tumors in female Sprague-Dawley rats as adriamycin or daunomycin (35,Table 7). 37 Table 7. 8 mg/kg a a 14 3 3 5 10 a a Compounds, gift of Dr. F. Arcamone, Farmitalia - Carlo Italy. v. injections of equally toxic doses. b Observation period, one year. 20 rats per group. Erb~ The agent was shown to intercalate into DNA with an affinity equivalent to that of daunomycin (36). As our studies show, the agent is also a mutagen in a bacterial mutagenesis assay with the strain TA98 of Salmonella typhimurium (Table 8).
5 4'-deoxyDX 4 4'-0-methylDX 4 6 6 inhib. d 119,186 175,186 229,142 162,248 >278,273 >278,171 157,244 >278,288 74,61 95,95 94,76 98,98 91,89 97,96 91,89 94,99 . e TOXlClty 0/6 13/16 1/6 11/16 0/6 10/16 0/6 6/16 (a) Data of two experiments. v. q7d x 4, starting on Day 1 after tumor inoculation. (c) See Table 1. (d) See Table 2. (e) Evaluated in non-tumored mice, observed for 90 days. ~o dose-related tissue uptake studies have been carried out up to now, but it is rational to think that by increasing the dose, it is possible to increase the antitumor effect.
Anthracycline Antibiotics in Cancer Therapy: Proceedings of the International Symposium on Anthracycline Antibiotics in Cancer Therapy, New York, New York, 16–18 September 1981 by F. S. Philips (auth.), Franco M. Muggia, Charles W. Young, Stephen K. Carter (eds.)