Resveratrol (Res) has been reported to possess cancer chemopreventive activity on the basis of its in vitro effects on tumor cells and in vivo experimental models of rodents transplanted with parental tumors or treated with carcinogens. We investigated the effects of Res on the development of mammary tumors appearing spontaneously in HER‐2/neu transgenic mice at an early age. The mechanisms involved in the Res antitumor effect were evaluated by studying the immune effectiveness, tumor apoptosis and expression of mRNA and protein for HER‐2/neu in tumoral mammary glands from Res‐treated mice and in tumor cell lines. Res supplementation delayed the development of spontaneous mammary tumors (p < 0.001), reduced the mean number and size of mammary tumors (p < 0.0001) and diminished the number of lung metastases in HER‐2/neu transgenic mice. The effects of Res were associated with downregulation of HER‐2/neu gene expression and increased apoptosis both in tumoral mammary glands and in murine (N202) and human (SKBr3) tumor cell lines. Neither the basal, the IL‐2‐induced NK activity nor the lymphocyte number and proliferation was modified in Res‐supplemented compared to control mice. Our results demonstrate that Res supplementation delays the development and reduces the metastasizing capacity of spontaneous mammary tumors in HER‐2/neu transgenic mice. The antitumor effect of Res might be related to the downregulation of HER‐2/neu expression and the induction of apoptosis in tumor cells.

A good body of experimental and clinical results has supported the existence of numerous reciprocal interactions among the nervous, endocrine and immune systems. Increasing evidence has been accumulated in the last years on the interaction between pituitary-thyroid hormones and the immune system on the basis of either the existence of receptors for thyreotropic and thyroid hormones on lymphocytes or the frequent immune alteration in physiological and pathological fluctuations of thyroid hormones. The data were obtained either in animals with experimentally induced hyper- or hypothyroidism or in humans with various hyperthyroid or hypothyroid situations. Conversely, immune-derived products such as lymphokines and monokines have been shown able to influence the pituitary-thyroid axis modulating either the thyroid hormone levels or the hormone/cytokine production by thyrocytes. The present paper aims at summarizing the data available on the existence of thyroid-immune interactions, and at analyzing the possible integration between pituitary-thyroid hormones and immune factors in favoring the development and maintenance of both thymic and peripheral immune efficiency. The relevance of pituitary-thyroid-immune interactions is discussed for its implication in the ageing process.

Background/Aims: Head and neck squamous cell carcinoma (HNSCC) ranks sixth worldwide for tumor-related mortality. A subpopulation of tumor cells, termed cancer stem cells (CSCs), has the ability to support cancer growth. Therefore, profiling CSC-enriched populations could be a reliable tool to study cancer biology. Methods: We performed phenotypic characterization of 7 HNSCC cell lines and evaluated the presence of CSCs. CSCs from Hep-2 cell line and HNSCC primary cultures were enriched through sphere formation and sphere-forming cells have been characterized both in vitro and in vivo. In addition, we investigated the expression levels of Nicotinamide N-methyltransferase (NNMT), an enzyme overexpressed in several malignancies. Results: CSC markers were markedly expressed in Hep-2 cell line, which was found to be highly tumorigenic. CSC-enriched populations displayed increased expression of CSC markers and a strong capability to form tumors in vivo. We also found an overexpression of CSC markers in tumor formed by CSC-enriched populations. Interestingly, NNMT levels were significantly higher in CSC-enriched populations compared with parental cells. Conclusion: Our study provides an useful procedure for CSC identification and enrichment in HNSCC. Moreover, results obtained seem to suggest that CSCs may represent a promising target for an anticancer therapy.