By F. S. Philips (auth.), Franco M. Muggia, Charles W. Young, Stephen K. Carter (eds.)

F. M. MUGGIA whilst confronted with the inadequacies of present melanoma therapy, we like to examine what the longer term may possibly carry. in general, we take without any consideration the prior, who prefer examine into completely new parts. besides the fact that, the chronic improvement of fertile soil might yield amazing rewards when you decide to construct at the wisdom of the past--hence, this symposium on anthracycline antibiotics. even if the anthracycline antibiotics signify 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 scientific program of those compounds heralded a decade of pleasure between oncologists facing pediatric tumors, breast melanoma, leukemias, and lymphomas, and opened new wish for sufferers bothered with sar­ comas and numerous different tumors that were deemed - sistant to chemotherapy. those successes have been tempered with the belief that the antitumor influence of anthracyclines can be accomplished now and then simply on the very excessive expense of risking cardiac decompensation and, nearly continually, with the incidence of alopecia and different acute toxicities. This checklist of previous achievements and difficulties has slowly given approach to a gift more and more illuminated by way of our skill to switch the distressing toxicities of those brokers. specific medical experiences supplemented by means of inventive laboratory types have steadily elucidated mechanisms and danger elements 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

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Mutagenicity Adriamycin and daunomycin are clearly mutagenic in bacterial and mammalian cell assays. Adriamycin and daunomycin were shown to be active mutagens (without microsomal activation) in Salmonella typhimurium (30, 31, 32). In Saccharomyces cerevisiae, however, daunomycin though recombinogenic was not mutagenic (33). , both, adriamycin and daunomycin are potent mutagens in a mammalian cell mutagenesis assay employing V79 Chinese hamster cells (8). In this assa~ both antibiotics were as active as the standard mutagen, Nmethyl-~'-nitro-~-nitrosoguanidine.

In our studies with Salmonella typh. the agent (gift of Dr. L. Lenaz, International Div. , USA)proved to be mutagenic in strains TA98 and TA100 of Salmonella typh. with and without addition of rat liver S9. 4. Marcellomycin Marcellomycin is a new anthracycline antitumor antibiotic. We found this agent to be non-mutagenic in strains TA98 and TA100 of Salmonella typh. with and without addition of rat liver S9 (Table 14). Table 14. Surv. /Plate -S9 +S9 17 16 20 14 13 2 325 124 84 75 26 23 28 15 19 20 27 813 118 90 89 74 - >1,000 Procedures according to reference no.

This aspect should therefore be more deeply investigated. L1210 leukemia is rather resistant to ONR and OX therapy; the high effectiveness of 4-dmONR on this type of tumor stimulated researches on P388/0X (P388 leukemia resistant to OX). 4-0mONR is not active in vivo on this tumor line bearing acquired resistance to anthracyclines (26); however, in in vitro experiments, 4-dmONR has an interesting cytotoxic activity on P388/0X leukemia cells, as the ratio between I0 50 on P388/0X and I050 on P388, is 75 for OX, 85 for ONR, and 35 for 4-dmONR (50).

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