Biomedical subjects

T E Webb

Publications and source records attributed to T E Webb.

165 records · Page 10Linked to original sources

PubMedDate not supplied

In vivo use of N-(4-hydroxyphenyl retinamide)-0-glucuronide as a breast cancer chemopreventive agent.

The inhibitory effects of N-(4-hydroxyphenyl) retinamide and its glucuronide derivative on the development and growth of 7,12-dimethylbenz (a) anthracene - induced rat mammary tumors in vivo were compared. The results indicate that the glucuronide had a greater chemopreventive potency than equimolar concentration of the free retinoid by all the criteria measured, mainly the inhibition of tumor incidence, multiplicity and tumor growth. HPLC analysis of the blood of the rats showed no hydrolysis of the glucuronide during its chronic consumption, indicating that the retinoid glucuronide is probably acting in vivo per se rather than through hydrolysis to the free retinoid. The higher potency and lower toxicity of the glucuronide suggests, for the first time, that the conjugate may have an in vivo chemopreventive advantage over the parent retinamide.

9,10-Dimethyl-1,2-benzanthracene↗

PubMedDate not supplied

Mechanism of growth inhibition of mammary carcinomas by glucarate and the glucarate: retinoid combination.

In synergistic combination 0.75 mmol/kg diet of N-(4-hydroxyphenyl) retinamide and 32 mmol/kg diet of glucarate inhibits the growth of primary rat mammary tumors, but are equally effective as single agents at 1.5 and 128 mmol/kg diet, respectively. Dose-response studies suggest that like retinoids, glucarate acts directly on tumor cells, rather than having an adjuvant effect. Although synergism is maintained down to at least 0.38 mmol/kg diet of the retinoid, experiments using Vitamin A-deficient diets indicates 128 mmol/kg glucarate acts independent of retinoid. Both alone and in combination, glucarate and retinoid inhibited the growth of human mammary tumor cells grown in the athymic mouse, the growth of rat mammary tumors in germfree rats and the hormone-independent MTW 9a/R rat mammary tumor. Like retinoids, glucarate suppresses protein kinase C and induces transforming growth factor-beta, in the mammary tumor cells.

9,10-Dimethyl-1,2-benzanthracene↗

PubMedDate not supplied

Basis for the anti-tumor and chemopreventive activities of glucarate and the glucarate:retinoid combination.

The biochemical basis for the cancer chemopreventive and anti-cancer activities of glucarate, retinoids (13-cis-retinoic acid, hydroxyphenyl retinamide) and their synergistic combination, has been evaluated. Neither alone nor in combination did these agents affect the level in the rat, of enzymes which are (a) known to correlate with reduced risk of carcinogenesis (detoxification enzyme, catalase, glutathione reductase) nor (b) enzymes which correlate with increased risk of carcinogenesis (beta-glucuronidase, xanthine oxidase, glucose-6-phosphate dehydrogenase). Retinoids, but neither glucarate nor its lactone inhibited free radical-induced lipid peroxidation. Both agents alone and synergistically in combination, raise cellular cAMP levels, repress protein kinase C and more generally inhibited DNA synthesis.

Animals↗