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PubMed1979

Incidence and pathological features of spontaneous tumors in athymic nude mice.

Systematic observation of 1141 nude mice (Swiss background [corrected] strain) that received human tumor transplants revealed 24 spontaneous tumors, 18 of lymphoreticular origin and 6 pulmonary adenomas. Spontaneous tumors were seen at an average age of 9.1 months, and 22 of the tumors were seen only in that fraction of our group (324 mice) surviving for 5 months or more (22 of 324 X 100 = 6.8%). Transplantation of these tumors to other nude mice was successful in three of five cases. Mice transplanted with adenocarcinoma of the colon and with tumors of the urogenital tract developed spontaneous tumors more often than did mice receiving other types of human tumor transplants. Progressive growth of the human tumor transplant occurred significantly less often in the mice that eventually developed spontaneous tumors than in the mice that showed no spontaneous tumor development. Nevertheless, the incidence of spontaneous tumors in these nude mice was similar to that reported for the thymus-bearing background strain.

Adenoma↗
PubMed1979

Experimental evaluation of anthracycline analogs.

This review summarizes the preclinical tests conducted to date for experimental evaluation of new anthracycline analogs. Most of the data are derived from the experience at the Istituto Nazionale Tumori, Milan, Italy, at the National Cancer Institute, Bethesda, Md, and at the Farmitalia Research Laboratories, Nerviano, Italy. In vitro cytotoxicity tests are useful for determining the doses to be used in vivo. Antitumor activity tests in mice can be divided into different stages. P388 and L1210 leukemias are generally used in primary screening; the value of adding L1210 leukemia is briefly discussed. Other experimental tumors adopted include disseminated leukemia and transplanted solid tumors. The importance of the route and schedule of treatment is stressed. Drugs should be administered iv in the case of solid tumors, and the schedule of treatment can be adjusted according to the pharmacokinetic properties of the new analog, when these are known. If possible, the parent compound and the new analog should be dissolved in the same solvents. In the toxicity tests, cardiac toxicity deserves particular attention. Until now, the only experimental model in which a number of new anthracyclines have been tested is the rat model proposed by Zbinden. A comparison between cardiotoxicity data obtained in such models and antitumor data obtained in mice shows that cardiac toxicity can be dissociated from the antitumor activity. Knowledge of pharmacokinetic properties of new analogs is of importance for selecting the schedules of treatment and for explaining selective toxic effects.

Animals↗