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Sodium butyrate at a 5 mM concentration prevents the induction of tyrosine aminotransferase in hepatoma culture cells, without affecting the basal level of the enzyme. This effect is reversible immediately after the removal of butyrate, or after a lag, if butyrate was present for more than 2 h.Neither the amount of cellular RNA nor the rate of total RNA synthesis were affected by sodium butyrate. Furthermore butyrate does not inhibit protein synthesis : [35S]methionine incorporation into proteins, measured in a reticulocyte lysate system, shows no significant difference between the translation capacity of the RNAs from butyrate-treated cells and from dexamethasone-induced or uninduced cells. Nevertheless, when tyrosine aminotransferase was isolated from the translation products by its specific antiserum and analyzed by gel electrophoresis, we observed that the amount of the enzyme synthesized in the presence of RNAs from dexamethasone/butyrate-treated cells was strongly diminished relative to that synthesized in the presence of RNA from dexamethasone-induced cells. These experiments indicate that the treatment of the cells with butyrate decreases the activity of the specific messenger RNA for tyrosine aminotransferase to a level close to the basal level.Butyrate does not prevent the penetration of the hormone and has a limited effect on the translocation of the glucocorticoid-receptor complex to the nucleus.We therefore conclude that the effect of sodium butyrate might be inherent either to an impairment of an early step of the hormone-chromatin interaction or to an alteration of the transcription process of some specific genes. The rapidity and the complete reversibility of the effects of butyrate suggest that it does not irreversibly alter the structures which are the targets of its action.

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Background: Novel immune therapies targeting tumor specific antigens are being developed. Our purpose was to determine expression of the cancer testes antigen NY-ESO-1 in renal cell carcinoma (RCC), as NY-ESO-1 targeting approaches, particularly adoptive cell therapy, have not been evaluated in this disease.Methods: We employed tissue microarrays containing >300 unique RCC cases and adjacent benign renal tissue to determine NY-ESO-1 expression using a quantitative immunofluorescence method. In addition, we studied NY-ESO-1 expression in 35 matched primary and metastatic RCC specimens to assess concordance between different tumor sites.Results: NY-ESO-1 was highly expressed in a subset of RCCs. Expression in primary RCC specimens was significantly higher than adjacent normal renal tissue (P<0.0001) and higher in clear cell carcinomas than papillary RCC (P<0.0001). Expression levels in metastatic specimens were higher than in matched primary samples (P=0.0018), and the correlation between the two sites was modest (χ2=3.5, p=0.06).Conclusions: Aberrant NY-ESO-1 expression seen in clear cell RCC suggests that NY-ESO-1 targeting approaches should be studied in this disease. Expression is higher in metastatic sites, and discordance between primary and metastatic sites in some patients suggests that patient selection for these therapies should be based on expression in metastatic rather than nephrectomy specimens.

Melanoma is the leading cause of fatal skin cancer, and in the past few decades, there has been an increase in the incidence of and mortality from metastatic melanoma. Until recently, the therapeutic options for treatment of metastatic melanoma were limited. The approval of ipilimumab (an anti-CTLA-4 antibody) and vemurafenib (mutant B-RAFV600E kinase inhibitor) by the Federal Drug Administration has led to a new era in melanoma treatment, and additional promising drugs and drug combinations are currently being investigated. As the choices of treatment for melanoma have expanded, the need to identify predictive biomarkers to tailor treatment strategies to individual tumor or immune system characteristics has become necessary. Such strategies have the potential of maximizing antitumor effect while minimizing toxicity and improving clinical benefit. In this article, we review the currently approved targeted therapies in melanoma and discuss the future of personalized therapy for this disease.

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The effects of several antagonists of glucocorticoid action on a line of hepatoma cells (HTC strain) have been studied in order to determine their mechanisms of action. The induction of tyrosine aminotransferase by dexamethasone can be partially or totally inhibited if an antagonist is added simultaneously with dexamethasone or some time later. Antagonists, even if they have as much affinity for the cytoplasmic receptor as dexamethasone, must be administered at a 100-fold excess as compared to dexamethasone. Their receptor binding kinetics are not identical to those of inducer steroids: moreover there is no correlation between relative binding affinities and anti-inducing capacities. A short contact between the cells and the antagonist is sufficient to obtain a full antagonistic effect, but the antagonist is inactive if administered and removed from the cells before induction. An interpretation if suggested, considering these results which do not find a satisfactory explanation in the classical theory of receptor action.