Reticuloendothelial tumour

Methylisocytosine (LVIII, superacyl) has been reported to stimulate antibody production in rabbits to an extent greater than with a vaccine alone [354]. It also markedly reduced the development of pulmonary adenoma at 100 mg/kg per day for 10, 25 or 50 days s.c. or p.o. to mice, following a single i.p. injection of urethan. 5-Hydroxy-6-methylisocytosine had the same effect [19]. In tests on the effect of pyrimidines on reticuloendothelial functions in mice, the absorptive capacity of this system increased with 5-(hydroxymethyl)uracil or with 6-methylisocytosine. The effect was most pronounced when superimposed on cortisone inhibition [355]. When administered subcutaneously to mice, 6-methylisocytosine increased the inhibitory effect of thio-TEPA on the growth of Ehrlich tumours in mice. It is believed that this pyrimidine prevents the development of metastases [356]. 

Hepatocellular carcinomas and reticuloendothelial neoplasms of the Uver and adenomas and undifferentiated tumours of the kidney were induced in rats by feeding cycad material and the close resemblance of those tumours to those induced by di-methylnitrosamine was emphasised (Laqueur et al. 1963). 

To determine if paclitaxel monolglutamate was detectable as a metabolite in vivo, a series of tumours explants were extracted and assayed 24 hours after a single intravenous dose of CT-2103 (Figure 5A). As seen in Figure 5B, increasing amounts of the paclitaxel-monoglutamate were detected over several days in HT-29 colon cancers. Similar data were obtained from analysis of liver and spleen, suggesting that reticuloendothelial cells aie also able to break down CT-2103 by a similar mechanism. ... 

Taken in sum, these data suggest that the CT-2103 is taken up by tumour tissues and cells within the reticuloendothelial system. Free pacKtaxel is slowly released following cleavage of the PG backbone by cathepsin B. In circulation, CT-2103 does not release paclitaxel in appreciable quantities. An important parameter for a successful pol5mieric conjugate is a slow rate of release only outside of circulation. This spates normal organs high levels of exposure to free pacUtaxel... 

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