Anti-thyroid cancer properties of a novel isoflavone derivative, 7-(O)-carboxymethyl daidzein conjugated to N-t-Boc-hexylenediamine in vitro and in vivo.

The incidence of thyroid cancer is up to 3 folds higher in women than in men, suggesting that estrogenic effects may be involved in the pathogenesis of this malignancy. Here, we explore whether or not human thyroid cancer cell growth can be curbed by a novel isoflavone derivative generated in our laboratory, the N-t-Boc-hexylenediamine derivative of 7-(O)-carboxymethyl daidzein (cD-tboc). With the exception of the follicular cancer cell line WRO, estrogen receptor (ER)α mRNA was only marginally expressed in cell lines derived from papillary (NPA), follicular (MRO), anaplastic thyroid carcinoma (ARO) such that the expression of estrogen receptor (ER) ßmRNA was more abundant than that of ERα mRNA in these cell types. Estradiol-17ß (E2; 0.03-300nmol/l) per se increased proliferation in all four cell-types. The ERß-specific agonist DPN increased [(3)H]-thymidine incorporation in all four thyroid cancer cell lines, whereas the ERα-specific agonist PPT increased growth only in NPA and WRO. By contrast, cD-tboc, derived from the weak estrogen daidzein, did not cause cell growth and dose-dependently diminished cell growth in all four cell lines via apoptosis and not necrosis, as detected by the release of histone-DNA fragments. The cytotoxic growth inhibitory effect of cD-tboc in these cells was modulated by E2 and the general caspase inhibitor Z-VAD-FMK, and the magnitude of this salvage was cell type-and dose-dependent. When nude mice carrying ARO thyroid xenografts were treated with cD-tboc, tumor volume decreased significantly, and no apparent toxicity was observed. These results suggest that cD-tboc may be a promising agent for therapy of thyroid carcinoma either alone or in combination with existing cytotoxic drugs.

Thyroid cancer, thyroiditis and dietary iodine: a review based on the Salta, Argentina model.

Factors that should be considered when studying the effect of dietary iodine in the development of thyroid cancer include pathological criteria, diagnostic techniques, screening programs, radioactive fallout, and standard of medical care in the studied population. In most surveys, papillary carcinoma forms the largest group of thyroid malignancies, both before and after iodine prophylaxis where an increase in the papillary:follicular carcinoma ratio is also noted. Undifferentiated carcinomas decrease after salt prophylaxis. In Salta, Argentina, the increasing incidence of clinically significant papillary thyroid cancer and the decrease of undifferentiated carcinoma after iodine prophylaxis are probably due to better access to health centers and consequent earlier detection of differentiated precursor tumors. Autoimmune focal and diffuse or Hashimoto's thyroiditis are linked to dietary iodine. Pathological studies made in different regions indicate that these types of thyroiditis occur more frequently in areas of iodine sufficiency than in areas of iodine deficiency, and increase after iodine prophylaxis both in non-goitrous and iodine-deficient areas like Salta, Argentina. An increase of lymphocytic thyroiditis could be linked to an increased incidence of primary thyroid lymphoma, and thyroiditis is more commonly associated with papillary carcinoma than with other types of thyroid follicular or C-cell derived carcinomas regardless of iodine intake.

Thyroid papillary microcarcinoma: a descriptive and meta-analysis study.

The authors review anatomical, clinical characteristics and prevalence of thyroid microcarcinoma. Diagnostic procedures and risk factors of aggressiveness at diagnosis and during follow-up are also covered. The possible clinical, pathologic and therapeutic risk factors are analyzed by meta-analysis study. Treatment procedures by different authors and guidelines suggested by societies are reported.