Analysis of correlation between the process of thyroid fibrosis and TGFB1 gene expression level in fine-needle aspiration biopsy (FNAB) thyroid specimens collected from patients with Hashimoto's thyroiditis and non-toxic goitre.

Transforming growth factor beta 1 (TGFB1) stimulates the production of various extracellular matrix components; at the same time, it inhibits matrix degradation. These actions of TGFB1 contribute to tissue repair, however, an altered expression of TGFB1 can be a causative factor of fibrosis processes, including thyroid fibrosis which follows chronic thyroiditis. The aim of our study was to examine a potential correlation between TGFB1 gene expression level in fine-needle aspiration biopsy (FNAB) thyroid specimens and fibrosis of the thyroid gland in two types of thyroid lesions. Fibrosis of the thyroid tissue was assessed, based on the expression levels of fibrosis-associated genes (COL1A1 and COL3A1) in thyroid FNAB samples, on the FNAB specimen cellularity and other features of the tissue fibrosis assessed during cytological examination, as well as on the size of thyroid gland and its function. Following routine cytological examination, 63 thyroid FNAB specimens, received from patients with Hashimoto's thyroiditis (HT, n=30) and non-toxic goitre (NTG, n=33), were quantitatively evaluated regarding TGFB1, COL1A1 and COL3A1 expression level by real-time PCR in the ABI PRISM 7500 Sequence Detection System. The obtained results showed statistically significant differences regarding the expression level (RQ) of TGFB1 and of COL1A1 genes between the groups with HT and with NTG (higher expression in HT group). No significant differences, concerning the expression level of COL3A1 gene, were observed for the studied groups (HT vs. NTG). In HT group statistically significant correlation was found between TGFB1 gene and COL3A1 gene expression levels (p<0.05). The correlation in question might suggest excessive extracellular matrix deposition and could--possibly--contribute to thyroid fibrosis mechanism in the course of chronic thyroiditis.

Prevalence of RAS point mutations in papillary thyroid carcinoma; a novel mutation at codon 31 of K-RAS.

The aim of this study was to assess the incidence of point mutations in RAS oncogenes of papillary thyroid carcinoma (PTC). Tumour specimens were obtained from 29 PTCs. The fragments of exons 1 and 2 of RAS oncogenes family (H- RAS, K- RAS, N- RAS) were amplified and then, point mutations were detected by SSCP and/or by RFLP analysis. Several DNA samples were directly sequenced to confirm the results. Two mutations were found in this study (GAA/CAA at codon 31 of K- RAS and CAA/CAC at codon 61 of N- RAS oncogene). These data confirm the results of previous studies, showing that RAS mutations are more rarely found in PTC than in follicular neoplasms. The influence of a novel mutation at codon 31 of K- RAS oncogene on the development of PTC needs further studies.

Gonadotropin-releasing hormone (GnRH) receptors in tumors: a new rationale for the therapeutical application of GnRH analogs in cancer patients?

Gonadotropin-Releasing Hormone (GnRH) is the hypothalamic decapeptide which plays a key role in the control of reproductive functions. By binding to specific receptors present on the pituitary gonadotropes, GnRH regulates gonadotropin release and, consequently, steroid hormone secretion from the gonads. When given continuously and at high doses, GnRH agonists suppress the pituitary gonadal axis through the down-regulation and desensitization of its own receptors. Based on this rationale, pituitary GnRH receptors represent the target for the successful utilization of GnRH agonists (that are more stable than the native peptide) for the treatment of hormone-dependent tumors (e.g., prostate, breast, endometrial, ovarian cancers). The observation that GnRH receptors are expressed in steroid-dependent tumors, and that their activation reduces cell proliferation and metastatic behavior of cancer cell lines, both in vitro and in vivo (when inoculated into nude mice), indicates a possible additional and more direct antitumor activity for these compounds. Interestingly, GnRH receptors have been shown to be expressed also in androgen-independent prostate carcinoma, as well as in tumors that are not classically considered hormone-related (e.g., melanoma), suggesting a clinical utility of the administration of GnRH analogs also in these tumors. More recently, GnRH agonists have been proposed as useful carriers to target cytotoxic drugs or toxins to cancer cells displaying the specific GnRH receptors. A second form of GnRH (designated GnRH-II) has been discovered in most vertebrates, including humans. GnRH-II has been suggested to act through a 'putative' cognate type II GnRH receptor, which is distributed in different tissues, both normal and tumoral. In humans, a full-length functional type II GnRH receptor has not been found. Therefore, its functions as well as its possible utility as a molecular target for a GnRH-II based therapy in oncology still has to be clarified. This review will focus on the role of GnRH receptors in the control of tumor growth, progression and dissemination. It will also be discussed whether the presence of these receptors might represent an additional rationale for the clinical utility of GnRH analogs as anticancer drugs.