New daunorubicin-protein conjugates were prepared by covalently linking the antitumor drug to various test proteins via its methylketone side chain. Attachment of daunorubicin to proteins was achieved by nucleophylic substitution reaction of the 14-bromo derivative of the drug, under mild coupling conditions. In contrast to conventional methods, this procedure did not involve reaction or modification of the amino sugar. As expected, the covalent linkage of the drug was generally associated with an appreciable reduction in the drug cytotoxicity to HeLa cells in vitro. The possible advantages of this method for coupling to specific protein carriers are discussed.
The pharmacokinetic of 4'-deoxydoxorubicin, a new analog of doxorubicin, was compared with that of its parent compound in mice treated with equal and equiactive doses. The levels of total fluorescence due to the initial drugs and to metabolites were determined in tissue extracts by fluorometry. 4'-Deoxydoxorubicin reached the same tissue levels as doxorubicin in all the organs tested except in spleen and lung, where a higher peak was found in the animals treated with the new analog. The rate of elimination of 4'-deoxydoxorubicin from the organs tested was higher than that of doxorubicin.
This paper describes the effect of Tween 80 on the antitumor activity and on the distribution of adriamycin in mice. The dilution of adriamycin in a 10% water solution of Tween 80 produced a significant increase of the antitumor activity in mice against ascites tumors (L 1210 leukemia), disseminated leukemias (transplanted leukemias originally induced by Gross leukemai virus and Moloney leukemia virus), and solid tumors (Sarcoma 180, MS-2 sarcoma). In all these experiments the drug was administered i.v., according to different schedules. Higher antitumor activity at the optimal dose and an increase of activity at lower doses were observed in different experimental systems. Toxicity was also slightly enhanced. Tissue distribution was studied in normal mice and in tumor-bearing mice (Gross leukemia and MS-2 sarcoma). In animals give i.v. adriamycin diluted in 10% Tween 80 there was a higher drug concentration in spleen, lung and kidney than there was in mice given the drug in a water solution. In all the other organs examined (heart, liver, small intestine) and in the MS-2 tumor tissue, no significant increase was observed. In L1210 leukemia-bearing mice, i.p. treatment with adriamycin diluted in 10% Tween 80 resulted in a significantly higher toxicity than that which resulted from treatment with adriamycin in a wa ter solution; no increase of antitumor activity was observed.
Communications to the Editor to a stirred, near boiling solution of 7.35 g (0.03 mol) of l-(5phenyl-4-oxo-2-oxazolin-2-yl)piperazine and 3.34 g (0.033 mol) of EtgN in 250 ml of CeH6. The mixture was refluxed for 1 h and, after cooling, the solid was filtered and washed with H2O. The CgHg filtrate was evaporated in vacuo leaving a solid residue. The combined solids were purified by recrystallization.l-(Phenylcarbamoyl)-4-(5-phenyl-4-oxo-2-oxazolin-2yl)piperazine (4d). A solution of 2.38 g (0.02 mol) of phenyl isocyanate in 5 ml of dioxane was added dropwise to a stirred, hot solution of 4.9 g (0.02 mol) of l-(5-phenyl-4-oxo-2oxazolin-2-yl)piperazine in 150 ml of dioxane. The mixture was refluxed with stirring for 1 h and evaporated to dryness in vacuo and the residue was recrystallized. Compounds 4e and 4f were similarly prepared.
Choroid plexus papillomas are very rarely reported neoplasms in both the surgical and radiological literature. The authors present their series of 7 papillomas and 1 carcinoma. They review the recent and former literature with the aim of demonstrating the role and usefulness of radiotherapy.
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