Endocrine Abstracts

Medullary thyroid carcinoma (MTC) is a malignant tumour deriving from parafollicular C cells, with a highly chemoresistant phenotype. Failure of medical therapy has been ascribed, at least in part, to multi drug resistance (MDR1) gene over-expression. MDR1 encodes for a transmembrane glycoprotein, P-gp, which hampers intracellular accumulation of cytotoxic drugs. It has been demonstrated that P-gp expression and function depend on cyclo-oxygenase 2 (COX-2) expression, which is...

: Magmas, a gene encoding for the mitochondrial import inner membrane translocase subunit, Tim16, protects different cell lines from the antitumoral effects of several pro-apoptotic stimuli (i.e. chemicals and chemotherapeutic agents). The synthetic Compound 5 is capable of sensitizing chemoresistant tumor cells overexpressing Magmas to proapoptotic stimuli, indicating that this molecule may be useful to overcome tumor chemoresistance. The aim of our study was to evaluate whet...

Introduction: CDKN1B gene, which encodes a cyclin-dependent kinase (Cdk) inhibitor, regulates the progression throughout G1 to S cell cycle progression. CDKN1B loss-of-function germinal mutations cause the multiple endocrine neoplasia type 4 syndrome (MEN4).Objective: The aim of the study is the functional characterization of a new 4 bp deletion in CDKN1B 5′-UTR region, identified in an acromegalic patient.Materials and metho...

Protein kinase C (PKC) is a family of serine-threonine kinases that regulate many cellular processes including proliferation and survival. Previous evidence has shown that PKC is involved in the control of human medullary thyroid carcinoma (MTC) proliferation and survival by modulating apoptosis, with a mechanism that implicates PKCβII isoform and translocation in different subcellular compartments.In this study, we investigated the role of PKC&#948...

Introduction: Bronchial carcinoids (BCs), originating from endocrine cells dispersed in the respiratory epithelium, can be divided into typical (TBC) and atypical (ABC). TBC are less aggressive, smaller, and much less likely to metastasize, while ABC are more aggressive and metastasize. mTOR has a central role in regulating cell growth, metabolism, and apoptosis. A differential mTOR activation in BCs has been previously demonstrated, suggesting that mTOR pathway might play a p...

GH and insulin-like growth factor 1 (IGF1) are known to promote breast carcinogenesis. Breast cancer (BC) incidence in not increased in female acromegalic patients, but mortality is greater as compared to general population. We previously demonstrated that GH/IGF1 excess influences BC response to therapy, possibly accounting for the increased mortality. We indeed showed that GH and IGF1 induce cell proliferation of a BC cell line, the MCF7 cells, providing protection towards t...

It has been demonstrated that everolimus, an mTOR inhibitor, has potent anti-proliferative effect in a human Medullary Thyroid Carcinoma (MTC) cell line, TT, and in two human MTC primary cultures. We aimed at evaluating the possible antiproliferative effects of everolimus in a group of 20 human MTC in primary culture. To this purpose, 20 MTCs were dispersed in primary cultures, treated without or with 1 nM – 1 μM everolimus, 10 nM SOM230, and/or 50 nM IGF1. Cell viab...

Many studies demonstrated that somatic BRAF gene mutation analysis increases diagnostic accuracy for papillary thyroid carcinoma (PTC), even from very small samples. The gold standard for point mutations research is direct sequencing, that implies DNA extraction, PCR with specific primers, sequencing reaction and run on an automatic sequencer. This is an expensive and time consuming method, and the possible contamination with wild-type DNA not coming from the nodule significan...

Familial pituitary adenoma is frequently associated with germinal mutations of several genes, including menin gene. MEN1 syndrome is an autosomic dominant disease, characterized by parathyroid adenomas, endocrine gastroenteropancreatic tumors, and pituitary adenomas, due to inactivating mutations of the MenI gene (11q13). MEN1 mutations are scattered within and around the menin open reading frame and are mainly represented by single nucleotide polymorphisms (SNPs), and ...

Pituitary tumour transforming gene 1 (PTTG1) is over-expressed in a variety of endocrine-related tumors. We investigated PTTG1 expression in human C-cell hyperplasia (CCH), human medullary thyroid carcinoma (MTC) and in the human MTC cell line, TT. PTTG1 expression was significantly higher (P<0.01) in CCH (threefold), in papillary thyroid cancer and in MTC (fivefold) than in normal thyroid, and in MTC lymph-node metastases as compared to primary lesions (approximate...