Endocrine Abstracts

Background: Bronchial carcinoids (BC) are still orphan of medical therapy. We previously demonstrated that the typical BC human cell line NCI-H727 is sensitive to Everolimus, in terms of cell viability reduction, while the atypical human BC cell line NCI-H720 is not. However, the mechanisms underlying this phenomenon have not been fully clarified.Aim: The aim of our study is to investigate the mechanisms of resistance to mTOR inhibitors in BC cells.<...

Adrenocortical cancer (ACC) is a rare and aggressive malignancy. Currently the main therapeutic option is surgery, but due to difficult and delayed diagnosis and to the onset of metastases, medical therapy is often tried. ACC treatment is mainly represented by Mitotane alone or in association with chemotherapy, with variable results. Understanding the molecular mechanisms that regulate ACC proliferation could be useful to identify new therapeutic options. Aim of our study is t...

It is well established that most TSH effects on the thyroid gland, including stimulation of proliferation, thyroid hormone synthesis and expression of thyroid-specific genes, are transmitted mainly by the adenylate cyclise pathway. However, in human follicular cells and in rat FRTL-5 cells, TSH can also stimulate the β-isoforms of PLC that catalyzes the hydrolysis of phosphatidyl-inositol 4,5-phosphate, yielding the second messengers DAG and inositol 1,4,5-phosphate facil...

Protein kinase C (PKC) is a key enzyme which regulates proliferation, apoptosis and differentiation, representing a pharmacological target for tumor therapy. PKC is a serin/threonin kinase involved in the control of neoplastic transformation, carcinogenesis, neoplastic invasion, chemoresistance. The role of PKC depends on the tissue and on the specific isoform, among the 11 identified so far. In particular, PKC beta II inhibits cell functions, while PKC delta has a protective ...

Adrenocortical cancer (ACC) is still orphan of medical treatment. Our preliminary data show that EGF induces ACC cell lines proliferation (+20 and +10% vs control in SW13 and NCI-H295 cell lines respectively). EGF receptor (EGFR) expression is higher and ubiquitous in SW13 cells, while it is weaker in NCI-H295 cells, where it is present only on the membrane. Aim of our study is to analyze EGFR downstream signalling in ACC cell lines.EGF induces VEGF synt...

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...

Everolimus (RAD001), an immunosuppressant drug, has antineoplastic activity in human neoplasia, including endocrine tumors, due to its ability to inhibit the AKT down-stream signaling pathway. It has been demonstrated that AKT is overexpressed and up-regulated in pituitary tumor, including ACTH-producing pituitary tumors, that are still orphan of an effective medical therapy. We therefore investigated the effects of RAD001 on cell viability, apoptosis and mTOR phosphorilation ...

GH and insulin-like growth factor 1 (IGF1) are known to promote breast carcinogenesis. Even if breast cancer (BC) incidence in not increased in female acromegalic patients, mortality is greater as compared to general population. In order to evaluate whether GH/IGF1 excess might influence BC response to therapy, accounting for the increased mortality, we evaluated the effects of GH and IGF1 on cell proliferation of a BC cell line, the MCF7 cells, in the presence of doxorubicine...

Effective medical therapy for persistent/recurrent medullary thyroid carcinoma (MTC) is not available, yet. Everolimus (RAD001) is a Rapamycin derivative, a potent mTOR pathway inhibitor. RAD001 has been employed in several clinical studies demonstrating antiproliferative and apoptotic effects in human tumors, both in vitro and in vivo, also in combination with somatostatin analogs. The aim of our study was to investigate the antiproliferative effects of RAD001 i...

Background: Bronchial carcinoids (BCs) are rare neuroendocrine tumors that are still orphan of medical treatment. Human BC primary cultures may display resistance to everolimus, an inhibitor of the mammalian target of rapamycin (mTOR), in terms of cell viability reduction.Aim: To assess whether the novel dual PI3K/mTOR inhibitor, NVP-BEZ235, may be effective in everolimus-resistant human BC tissues and cell lines. In addition, we search for possible mark...