Antitumor Tests

The mean survival times of the treated mice (T) and of the control (C) were used to calculate the percentage increase in median life time over control 

For B16 melanoma, the m ian diameter of the tumors on the 12 and on the 14 day after the tumor graft were measured for the control and treated sets of mice this blind procedure does indeed enable us to appreciate the way in which a drug delays and/or inhibits the growing of a solid tumor. 

The antitumor tests were performed using the standard NCI protocols the leukemia or the melanoma was transplanted on the day D, and the drug was inoculated by i.p. route (except for (III) where i.p. and i.v. routes could be used) on the day D + 1 (monoinjection protocol) or within a QnD schedule (the same dose being injected at intervals of n days from the day D + 1). 

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In conclusion of these antitumor tests on murine L1210, P388 and B16 tumors, it might be pointed out that the most effective in each case was the hexaziridino-cyclotriphosphazene NgPjAzg whereas NjPjClg and N P Clg appear to be poorly active, at least under our experimental conditions. Such a result requires some comments in the light of the ideas developed above. 

We shall report here on the synthesis and the antitumoral tests against P388 and L1210 leukemias of the simplest term of the series, namely N3P3(MeAz)g (MeAz = 2-methyl aziridinyl) (Fig. 30). The EORTC code name of this drug was MYKOMET 63. 

SOF, SOPHi and SOAz are soluble in water and could consequently by used in 0.9% NaCl water solution for both toxicity measurements and antitumoral tests DISOF, having very poor solubility in water, was inoculated as a suspension in 4 0 aqueous hydroxypropylcellulose (Klucel J. F. Hercules Co.). 

Thus, systematic antitumor tests against P388 were performed on both male and female mice with the help of F. Spreafico s EORTC team in Milano and of the Otsuka Pharmaceutical Company (see below) in Osaka, Japan. Conclusions are presented in Fig. 37 which clearly shows that SOAz is definitely a hormonal-... 

The antiviral and antitumor activity as well as the lymphocyte activation and modulation of the sensitivity to bacterid endotoxine are biological effects of DIVEMA based on the modification of the immunological responsiveness of the organism. Because of its antitumor activity, DIVEMA has been included under the code number NSC 46015 in a broad antitumor testing. Later it was found that the original NSC 46015 preparation was polydisperse and more narrow fractions were used It can be concluded from these studies that the activation of macrophages to kill the tumor cells is the predominant if not the only mechanism of antitumor activity of DIVEMA This is very probably true for many other synthetic polymers that... 

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