Preclinical evaluation of the anti tumour activity of new epoxyde derivatives.

As a follow-up to our initial results on the antineoplastic activity of alpha-1,3,5-triglycidyl-s-triazinetrione (alpha TGT, NSC-296934, Teroxirone), many new epoxyde derivatives were tested against murine tumours, mostly against P388 leukaemia, to determine their antineoplastic role and to characterize their specific effect against tumour cells in vivo, as well as to select an analogue with higher anti-cancer properties and superior pharmacological properties. Triglycidyl urazol (TGU, NSC-332488) showed the highest therapeutic activity and a good level of water-solubility which makes this agent a good candidate for phase-one clinical trials.

[Participation of the stomach and small intestine in the mechanism of insulin secretion following oral glucose administration]. / Uchastie zheludka i tonkoi kishki v mekhanizme sekretsii insulina posle peroral'nogo vvedeniia gliukozy

In chronic experiments on 22 dogs, four of them having fistulas of oesophagus, stomach, and duodenum combined with artificial dissociation of stomach from duodenum, the per os and intraduodenal administration of glucose increased concentration of glucose and immunoreactive insulin in the peripheral blood, while intrastomach administration of glucose increased the immunoreactive insulin concentration alone. The data obtained suggest three phases of insulin mobilization: the first is due to neural mechanisms and occurs at the moment of contact between glucose and mucosa of the mouth, stomach, and duodenum; the second phase seems to be due to enterohormones and is activated by the contact between glucose and mucosa of the mouth, stomach, and duodenum; the third phase is associated with resorptive hyperglycemia which directly activates the B-cells.

[Nuclear estradiol receptors in several "non-target" organs of rats]. / Iadernye retseptory k éstradiolu v nekotorykh organakh-"nemisheniakh" krys

Some properties of the macromolecules of the KCl-extracts of the nuclei of the uterus, kidney, liver, testis and prostate, specifically binding estradiol (E2), were studied. These macromolecules of the uterus and the liver were found to be maximally extracted from chromatin by the 0.6 M KCl concentration. The capacity of the macromolecules of the uterine, kidney and liver nuclear extracts to bind E2 specifically is destroyed completely by pronase, but not by RNA-ASe and DNA-ase, pointing to the protein nature of these macromolecules. Only estrogenic compounds, but not testosterone, 5alpha-dihydrotestosterone, progesterone or corticosterone were capable to compete with H3--E2 for the E2--binding sites of the macromolecules of the nuclear extracts of all the organs investigaeted. It is assumed that macromolecules of the nuclei of the investigated nontarget organs specifically binding E2 are estrogen receptors.