Onconeural versus paraneoplastic antigens?

A hallmark of naturally occurring tumor immunity is the aberrant expression of so called "onconeural antigens" or "paraneoplastic antigens". At present, these two terms are used as synonyms for proteins which are normally expressed only in neuronal tissues, but in the process of carcinogenesis, they can be detected in tumors located outside the nervous system. As neuronal tissues are immunopriveleged zones, expression of these proteins in tumor cells can induce an autoimmune response, which manifests in the generation of autoantibodies and/or specific cytotoxic T-cells. Whether or not such immune responses necessarily lead to paraneoplastic syndromes or to a beneficial antitumor response or both is not fully understood. In this review we comprehensively summarize recent literature on paraneoplastic antigens including the corresponding neurological syndromes. A unified classification is proposed with "onconeural antigens" as collective term and a number of subgroups including the recently discovered cancer-retina antigens. Certain onconeural antigens can serve as paraneoplastic antigens under conditions which have yet to be defined, implying that the paraneoplastic function is not inherent to the antigen. The potential of onconeural antigens in cancer diagnostics and treatment strategies is discussed.

Regulation of gene expression by retinoids.

Vitamin A serves as substrate for the biosynthesis of several derivates (retinoids) which are important for cell growth and cell differentiation as well as for vision. Retinoic acid is the major physiologically active form of vitamin A regulating the expression of different genes. At present, hundreds of genes are known to be regulated by retinoic acid. This regulation is very complex and is, in turn, regulated on many levels. To date, two families of retinoid nuclear receptors have been identified: retinoic acid receptors and retinoid X receptors, which are members of the steroid hormone receptor superfamily of ligand-activated transcription factors. In order to regulate gene expression, all-trans retinal needs to be oxidized to retinoic acid. All-trans retinal, in turn, can be produced during oxidation of all-trans retinol or in a retinol-independent metabolic pathway through cleavage of ß-carotene with all-trans retinal as an intermediate metabolite. Recently it has been shown that not only retinoic acid is an active form of vitamin A, but also that all-trans retinal can play an important role in gene regulation. In this review we comprehensively summarize recent literature on regulation of gene expression by retinoids, biochemistry of retinoid receptors, and molecular mechanisms of retinoid-mediated effects on gene regulation.