Degradation of endothelial cell matrix collagen is correlated with induction of stromelysin by an activated ras oncogene.

A conditional expression system was established whereby the human K-ras, v-src, and v-mos genes were cloned into a conditional expression vector downstream of the dexamethasone-inducible mouse mammary tumor virus long terminal repeat. Rat-1 fibroblasts were transfected with these constructs and selected in medium containing G418. Cloned transfectants were isolated and characterized for absolute dependence on dexamethasone for expression of oncogene products and anchorage-independent growth in soft agar.

Differential release of active proteinase inhibitors by two rat mammary adenocarcinoma variants possessing different metastatic potentials.

The ability of tumor cells to express elevated levels of proteinases capable of degrading tissue matrix and basement membrane components in vitro has been correlated to their invasive and metastatic potential. Many in vitro invasion assays have been performed either in the presence of serum or with tumor cells that had been previously grown in serum. Since serum contains large amounts of active proteinase inhibitors, their presence could complicate interpretations.

Pharmacokinetics and tissue distribution of recombinant human alpha A, D, A/D(Bgl), and I interferons and mouse alpha-interferon in mice.

The pharmacokinetics and tissue distribution in mice of several recombinant human alpha-interferons [rHuIFN-alpha A, D, I, and A/D(Bgl)] as well as natural mouse alpha-interferon (MuIFN-alpha) were assessed following single intravenous injections. The serum profiles of rHuIFN-alpha A, rHuIFN-alpha D, rHuIFN-alpha A/D(Bgl), and MuIFN-alpha were similar, whereas those following rHuIFN-alpha I showed a much longer terminal elimination phase. Differences in elimination half-life, volume of distribution, and total body clearance between these IFNs were observed.

Use of 125I-interferons in pharmacokinetic and tissue distribution studies.

The in vivo fate of radiolabeled recombinant human leukocyte A interferon (125I-rIFN-alpha A) and intramolecular hybrid A/D (125I-rIFN-alpha A/D Bgl) were studied, following iv injection into CD1 mice. Trichloroacetic acid (TCA) precipitable radioactivity, as well as antiviral activity, were measured in sera and several organ extracts. The results obtained by bioassay were very similar to those obtained by measuring the TCA precipitable radioactivity.

Relationship between binding affinities to cellular retinoic acid-binding protein and in vivo and in vitro properties for 18 retinoids.

A new rapid assay has been developed for measurement of the binding of [3H]retinoic acid to cellular retinoic acid-binding protein. The assay, which uses activated charcoal for the separation of bound from unbound retinoic acid, was used to determine the concentration required to inhibit the binding of [3H]retinoic acid to cellular retinoic acid-binding protein by 50% for 18 retinoids with free carboxylic acid groups. Partially purified cellular retinoic acid-binding proteins isolated from rat testes and carcinogen-induced rat mammary tumors were used for these determinations.