Reports on the role of retinoids in cell metabolism can be traced back almost a century, when the then-unknown vitamin A present in dietary lipids was found to be essential for normal growth {McCollum and Davis 1913; Osborne and Mendel 1913}. Since then, the profound effect of retinoic acid IRA}, a derivative of vitamin A, on development and differentiation has been documented in numerous publi...

The predominant isomer of retinoic acid in the plasma of dairy cows during the periparturient period is 9,13-di-cis-retinoic acid. Because retinoic acids influence the activity of cells in a variety of tissues, including the immune system, the potential for this isomer to modulate the bovine immune system during the periparturient period must be considered. The present study examined the in vit...

In this issue of Clinical Cancer Research , Li et al. investigate the chemopreventive potential of the retinoid, LG100268 (1). The application of retinoids to cancer chemoprevention has a long history which predates the identification of retinoid receptors (2, 3). Early clinical trials evaluated vitamin A derivatives, such as 13-cis-retinoic acid (13-cis-RA), all-trans retinoic acid (ATRA), and...

We describe a rapid and simple procedure for the simultaneous quantitation of endogenous 13-cis-retinoic acid, all-trans-retinoic acid, and retinol by isocratic normal-phase HPLC with ultraviolet detection, in 0.5 mL of human plasma. A silica adsorption column was eluted with n-hexane:2-propanol:acetic acid (200:0.7:0.135 by vol) at 0.9 mL/min, and the effluent monitored at 350 nm. The arotinoi...

With great interest we have read the article by Marchetti et al. on oxidation and isomerization of retinoic acid (RA) isomers in vitro, which was published in this journal recently (1). However, there are misleading statements in that publication, which require clarification. For instance, more than the indicated “few studies” on the metabolism of 9-cis-RA exist. Among the literature not referr...

A chemoprevention study was conducted to evaluate the activity of 9-cis-retinoic acid (9-cis-RA) as an inhibitor of prostate carcinogenesis in male Wistar-Unilever (HsdCpb:Wu) rats. After pretreatment with a sequential regimen of cyproterone acetate (50 mg/kg/day for 21 days) and testosterone propionate (100 mg/kg/day for 3 days), groups of 40 rats received a single i.v. injection of N-methyl-N...

It has long been known that retinoids are necessary for normal embryogenesis. To understand the role of retinoids in this process, it is important to elucidate the retinoid signalling pathway. The retinoid signal transduction pathway consists of three major components: (i) the metabolism of biologically active retinoids, (ii) nuclear receptors which bind to and are activated by retinoids, and (...

The retinoid response is mediated by families of nuclear receptors, the retinoic acid receptors (RARs), and the retinoid X receptors. All-trans retinoic acid (RA) binds only RARs and induces its own metabolism. In contrast, 9-cis RA is a newly identified agonist for both RARs and retinoid X receptors. We undertook a dose-ranging study to examine the safety, clinical tolerance, and pharmacokinet...

Structure-activity relationships are summarized for 87 retinoids, using reversal of keratinization in the hamster tracheal organ culture system to measure biological activity. Classes of compounds evaluated include all-trans-retinoic acid and its esters, ring-modified analogs of all-trans-retinoic acid and its esters, side-chain-modified analogs of all-trans-retinoic acid and its esters, analog...