Endocrine Abstracts

Obesity, characterized by an abnormal body fat accumulation mainly caused by a chronic imbalance between energy intake and expenditure, is a massive public health problem. Targeting excessive fat deposition in adipose tissue and ectopic fat accumulation in skeletal muscle through promoting lipid oxidation pathway may represent a promising strategy to counteract obesity. This study aims at investigating the effects of cabergoline (CAB), a dopamine agonist, on adipose and skelet...

Cushing’s disease (CD), caused by an adrenocorticotropic hormone (ACTH)-secreting pituitary tumor, is the most common form of hypercortisolism. Pituitary surgery is the first-line treatment of CD and medical treatment is an alternative second-line approach to control cortisol excess. Long-term exposure to glucocorticoids (GC) downregulates the expression of somatostatin receptor type 2 (SSTR2) but not type 5 (SSTR5) in human and mouse ACTH-secreting tumor cell cultures; t...

HCC is a difficult-to-treat- cancer with poor prognosis. Despite EVOLVE-1 trial demonstrated that EVE did not improve overall survival in molecularly and clinically unselected patients with advanced sorafenib resistant HCC, in selected patients, the established antitumor effect of EVE could make this drug a potential adjuvant therapy. Unfortunately, the acquired EVE resistance due to the tumour adaptation to chronic drug use is a current challenge. VitD has been deemed as pote...

Chronic cortisol excess as a consequence of ACTH overproduction from a pituitary tumour is responsible for the development of Cushing’s disease (CD). The first-line treatment for CD is pituitary surgery, but medical treatment is an alternative second-line approach to control cortisol excess. Among pharmacological agents, the adrenal-blocking drug ketoconazole (KT), is able to control cortisol excess in the majority of patients with CD. During KT treatment, the adrenal blo...

HCC is one of the most common malignancies worldwide. Local approaches are generally preferred for patients whose disease is restricted to the liver. In patients with extrahepatic disease systemic therapy can be considered. Chemotherapy did not demonstrate convincing survival advantages in several trails for HCC patients. Presently, the kinase inhibitor sorafenib is the only approved systemic target therapy for the treatment of advanced HCC. Mitotane (dichlorodiphenildichloroe...

HCC is a difficult-to-treat- cancer with poor prognosis. The recent EVOLVE-1 trial demonstrated that EVE did not improve overall survival in molecularly and clinically unselected patients with advanced HCC resistant to sorafenib treatment. In selected patients, the well-established antitumor effect of EVE could make this drug a potential adjuvant therapy. Unfortunately, the acquired resistance to this molecule due to the tumor adaptation to chronic drug use is a current challe...

Endocrine-disrupting chemicals, including bisphenol A (BPA) may promote obesity. The role of 1,25-Dihydroxyvitamin D3 (VitD) in counteracting adipogenesis is still a matter of question. Thus, the current study aims to investigate whether and how VitD exposure during adipogenesis could prevent the BPA pro-adipogenic effect in adipocyte models: the mouse pre-adipocytes 3T3-L1 and the human adipose-derived mesenchymal stem cells (hAMSC). 3T3-L1 and hAMSC were treated with VitD (1...

The transcriptional activator Bmal1, reaching acrophase in the morning and bathyphase in the evening, is the main regulator of circadian clock. A mutual interaction between circadian clock and glucocorticoids (GCs) has been described as well as their implication in muscle metabolism. The current in vitro study aims at investigating Bmal1 involvement in muscle catabolism induced by GCs circadian exposure. To this aim, mouse myocytes C2C12 were serum-shocked to synchron...

In vitro studies suggest that glucocorticoids (GC) long-term exposure downregulates SSTR2 but not SSTR5 expression in human and mouse ACTH-secreting tumor cells (AtT20), limiting the efficacy of octreotide (OCT), a somatostatin-receptor ligand with high affinity for SSTR2, in the treatment of Cushing’s disease (CD). In AtT20, dexamethasone treatment increased miR-375 expression, whose analysis revealed a seed-sequence for SSTR2, supporting the hypothesis that exc...

Acquired resistance has limited the use of systemic molecular therapy in the management of hepatocellular carcinoma (HCC). Immunotherapy, alone and in combination with systemic molecular therapy, is now the first-line standard of care for HCC. The current in vitro study aims at investigating PER2 role in the HCC aggressiveness and drug resistance acquisition. Parental PLC/PRF/5, PLC/PRF/5 resistant to Everolimus (EveR) and to Sorafenib (SorR) cell lines were used. To evaluate ...