Searchable abstracts of presentations at key conferences in endocrinology

ea0041ep599 | Endocrine tumours and neoplasia | ECE2016

Dual targeting of PIK3/AKT/mTOR and IGF1/KRAS/BRAF pathways in an in vitro model of ovarian cancer: strategies for cell proliferation control

de Angelis Cristina , Galdiero Giacomo , Pivonello Claudia , Patalano Roberta , Bifulco Giuseppe , Di Spiezio Sardo Attilio , Alviggi Carlo , De Placido Giuseppe , Colao Annamaria , Pivonello Rosario

Ovarian cancer (OC) is the most lethal gynecological cancer. Debulking surgery and platinum-based chemotherapy are the cornerstone of OC management; however, after a partial initial response, tumors invariably relapse. Therapeutic approaches should account for interindividual heterogeneity since OC histiotypes show distinct genetic profile. A2780 cell line has been annotated as high grade serous ovarian cancer (HGSOC); nevertheless, recent research underlined that the genetic ...

ea0041ep620 | Endocrine tumours and neoplasia | ECE2016

Potential role of the adrenolitic drug mitotane in the treatment of hepatocarcinoma (HCC): effect on cell proliferation in HCC cell lines

Pivonello Claudia , Provvisiero Donatella Paola , Negri Mariarosaria , Di Gennaro Gilda , De Angelis Cristina , Simeoli Chiara , Patalano Roberta , De Martino Maria Cristina , Colao Annamaria , Pivonello Rosario

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...

ea0041ep628 | Endocrine tumours and neoplasia | ECE2016

Potential role of vitamin D in restoring sensitivity to mTOR inhibitors in hepatocellular carcinoma (HCC): 1,25(OH)vitamin D (VITD) reverts everolimus (EVE) resistance in a HCC cell line

Pivonello Claudia , Provvisiero Donatella Paola , Negri Mariarosaria , Di Gennaro Gilda , De Angelis Cristina , Galdiero Giacomo , Simeoli Chiara , De Martino Maria Cristina , Colao Annamaria , Pivonello Rosario

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...

ea0041ep712 | Male Reproduction | ECE2016

The role of dopamine pathway on human sperm: in vitro effect of dopamine receptor agonists and antagonists on sperm motility, kinetics and viability

de Angelis Cristina , Cariati Federica , Galdiero Giacomo , Coppola Giorgio , Galdiero Mariano , Salzano Ciro , Pivonello Claudia , Patalano Roberta , Alviggi Carlo , De Placido Giuseppe , Colao Annamaria , Pivonello Rosario

Dopamine has been found in both semen and oviductal fluid and dopamine receptors (DRs) have been detected in male genital tract and spermatozoa, suggesting that dopamine system may control important reproductive functions in humans. Dopamine improves sperm motility and viability in animal models, although the underlying molecular mechanisms have not been fully elucidated. The aims of this study were to investigate DRs expression in human spermatozoa and to evaluate the in ...

ea0037gp.01.03 | Adrenal | ECE2015

Effect of the switch from conventional glucocorticoids to ‘dual release hydrocortisone' in adult patients with primary and secondary adrenal insufficiency: a 6-month multicentre study

Pivonello Rosario , Simeoli Chiara , Isidori Andrea M , Ciresi Alessandro , Savastano Silvia , Auriemma Renata S , Graziadio Chiara , Di Somma Carolina , Giordano Carla , Lenzi Andrea , Colao Annamaria

Adrenal insufficiency (AI) requires life-long glucocorticoid (GC) treatment, which is associated with an increased risk of metabolic syndrome (MS), probably due to cortisol overexposure for multiple drug daily doses, together with an impairment of quality of life (QoL). Moreover treatment compliance (TC) is reported to be suboptimal in AI patients. The current study aimed at investigating the impact of the switch from twice/thrice daily conventional GCs to once daily dual-rele...

ea0037gp.19.08 | Pituitary–Acromegaly | ECE2015

Effects of long-term combined treatment with somatostatin analogues and pegvisomant on cardiac structure and performance in acromegaly

Auriemma Renata S , Grasso Ludovica F S , Galdiero Mariano , Pivonello Claudia , Salzano Ciro , Negri Mariarosaria , Angelis Cristina de , Colao Annamaria , Pivonello Rosario

Somatostatin analogues (SA) are known to revert acromegalic cardiomyopathy mainly in young patients with short disease duration, whereas pegvisomant (PEG) reportedly improves cardiac structure and performance in patients resistant to SA. To date, no data are available on the effects of long-term SA+PEG on cardiovascular complications. The current study aimed at investigating the effects of long-term SA+PEG on cardiac structure and performance in acromegaly. Thirty-six acromega...

ea0037ep48 | Adrenal cortex | ECE2015

The treatment with ‘dual release' hydrocortisone (DR-HC) in congenital adrenal hyperplasia: short-term (6 months) and long-term (12 months) follow-up after the switch from conventional glucocorticoids to DR-HC

Simeoli Chiara , De Martino Maria Cristina , Iacuaniello Davide , Mannarino Teresa , Cozzolino Alessia , De Leo Monica , Pivonello Claudia , Negri Mariarosaria , De Angelis Cristina , Colao Annamaria , Pivonello Rosario

In patients with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, life-long glucocorticoid (GC) treatment is often required to replace cortisol deficiency and to avoid the ACTH-dependent androgen levels increase. However, in these patients, the multiple daily doses required with conventional GCs can cause cortisol overexposure, leading to an increased risk of metabolic syndrome (MS), an impaired quality of life (QoL), and poor treatment compliance (TC). T...

ea0037ep94 | Adrenal cortex | ECE2015

Combined effects of sirolimus and mitotane in the inhibition of growth in human adrenocortical carcinoma cells

De Martino Maria Cristina , van Koetsveld Peter M , Feeldes Richard A , Lamberts Steven W J , de Herder Wouter W , Colao Annamaria , Pivonello Rosario , Hofland Leo J

Adrenocortical cancer (ACC) is a rare cancer with poor prognosis and scant treatment options. Mitotane alone, or in combination with cytotoxic chemotherapy, represents the referral current treatment for patients with unresectable ACC. Recent studies have shown that mTOR inhibitors suppress growth of ACC cells. This study aimed at evaluating the effects of mitotane in combination with mTOR inhibitors. In H295 and SW13 cells we tested the effects of a 6 day treatment with increa...

ea0035oc7.3 | IGF-1 and Thyroid Basic | ECE2014

Targeting the insulin-like growth factor 1 (IGF1R) and insulin (IR) receptor with a dual IGF1R/IR inhibitor, OSI-906, to potentiate mTOR inhibitor effects in experimental models of hepatocellular carcinoma (HCC)

Pivonello Claudia , Negri Mariarosaria , De Martino Maria Cristina , de Angelis Cristina , Napolitano Maria , Izzo Francesco , Colao Annamaria , Hofland Leo J. , Pivonello Rosario

The mTOR and IGF/insulin pathways are frequently dysregulated in HCC. Antitumoral activity of mTOR inhibitors (mTORi) has been demonstrated in experimental models but in early clinical studies mTORi alone have shown modest antitumoral activity. IGF/insulin-dependent Akt activation, via IGF1R and IR, has been suggested as potential mechanism for mTORi resistance. This study aimed at evaluating the expression of mTOR and IGF/insulin pathway components and the effects of mTORi al...

ea0035oc8.4 | Pituitary clinical | ECE2014

Normalization of urinary cortisol with the potent 11β-hydroxylase inhibitor LCI699 in patients with Cushing's disease: 22-week, multicentre, open-label study

Biller Beverly , Young Jacques , Hamrahian Amir , Fleseriu Maria , Molitch Mark , Pivonello Rosario , Shimatsu Akira , Shimizu Chikara , Tanaka Tomoaki , White Tracy , Hilliard Annie , Tian Chuan , Sauter Nicholas , Bertagna Xavier

Background: A proof-of-concept study (LINC 1) demonstrated that after 10 weeks, LCI699 normalized UFC in 11/12 patients with Cushing’s disease. This interim analysis of the first eight patients enrolled into a longer-term study (LINC 2) further evaluates LCI699 in Cushing’s disease; the full analysis on all 19 enrolled patients is expected in time for the congress.Methods: There were two study groups. Previous LINC 1 participants (follow-up coh...