The anti-tumor arotinoid Ro 40-8757 protects bone marrow from the toxic effects of cyclophosphamide.

The arotinoid Ro 40-8757 is a novel compound that has significant therapeutic activity against chemically induced breast tumors in rats. The results of combination therapy with cyclophosphamide, plus the arotinoid showed that the anti-tumor effects were additive. However, all of the rats given CPA alone died between week 6 and week 10 of treatment.

Comparison of the therapeutic effects of a new arotinoid, Ro 40-8757, and all-trans- and 13-cis-retinoic acids on rat breast cancer.

A novel arotinoid, 4-((2-(p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl- 2-naphthyl)propenyl]phenoxy))ethyl))-morpholine, was tested in rats bearing established chemically induced mammary tumors. At a dose of 0.35 mmol/kg/day of 4-((2-(p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2- naphthyl)propenyl]phenoxy)ethyl))-morpholine, decreased tumor growth was seen after 2 weeks.

The relevance of the mouse papilloma test as a predictor of retinoid activity in human psoriasis.

The combination of the results of mouse antipapilloma tests with those from hypervitaminosis A tests in mice as the basis for calculating a therapeutic index has been used for more than 20 years in the search for retinoids as useful drugs in human dermatology. A number of retinoids identified as active or inactive when administered systemically in these mouse systems have gone into clinical trials; clinical results on 11 retinoids were available for a retrospective analysis on the predictive relevance of the mouse models for retinoid activity in human psoriasis. This analysis revealed that the therapeutic index in mice correctly identified eleven compounds and differentiated them into markedly active, moderately active or inactive retinoids when subsequently used clinically in the treatment of various forms of psoriasis.

Therapeutic effect of the arotinoid Ro 15-0778 on chemically induced rat mammary carcinoma.

The arotinoid Ro 15-0778 (temarotene) is a third generation retinoid without a polar end-group. Established, palpable and measurable rat mammary tumours, chemically induced by oral administration of 12 mg/animal 7,12-dimethylbenz[a]anthracene, were treated with Ro 15-0778 as a feed-admix in daily doses of 100 mg/kg for 6 weeks and 200 and 400 mg/kg for 9 weeks. For comparison, tamoxifen (anti-oestrogen) was administered as a feed-admix in doses of 10 and 30 mg/kg/day for 9 weeks.

Preclinical safety testing of species-specific proteins produced with recombinant DNA-techniques. An attempt to transfer current experience into future testing strategies.

Preclinical toxicity studies in animals with species-specific recombinant DNA products have now been performed for several years. An interim statement on the significance of these animal tests and their ability to predict adverse effects in humans therefore appears indicated, with the aim of deducing future testing strategies. The experience accumulated so far shows that the animal models have failed to predict adverse effects subsequently observed in man.

Reversible, retinoid-induced secretion of canine ceruminous glands.

The long-term (12 months) oral administration of the aromatic retinoid Ro 10-1670 (etretin) to dogs in relatively high doses of 5.0, 15.0 and 50.

Ro 15-1570, a new sulfur-containing retinoid devoid of bone toxicity in rats.

Repeated ingestion of high doses of retinoids cause the so-called hypervitaminosis A syndrome. In rats the main symptoms are weight loss, alopecia, erythema, desquamation of the skin, and alterations of the skeletal system, including bone fractures. In the present study, three retinoids (Ro 15-1570, arotinoid ethylsulfone, 6 mg/kg; retinoic acid, 100 mg/kg and etretinate, 50 mg/kg) were administered orally to rats for 1 and 2 weeks, respectively, to six male and six female rats/group.

Preclinical safety evaluation of intravenously administered mixed micelles.

Mixed micelles, with their main constituents lecithin and glycocholic acid, form a new principle for the parenteral administration of compounds which are poorly water-soluble. Their composition of mainly physiological substances as well as their comparatively good stability substantiate their attractivity in comparison to existing solvents. A decomposition due to physical influences such as heat or storage for several years will almost exclusively affect the lecithin component in the form of hydrolysis into free fatty acids and lysolecithin.

The short term fate of dischargeable glass beads implanted surgically in the mouse urinary bladder.

Although both male and female mice of different ages expelled surgically implanted glass beads with diameters of 1 mm and 0.5 mm within 5 weeks in comparable numbers, urinary stones formed in relation to these implanted beads more frequently in male mice than in females. This stone formation in male mice may be a consequence of the relatively high mucoprotein content in the urine of the male mouse.