Searchable abstracts of presentations at key conferences in endocrinology

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...

ea0070aep671 | Pituitary and Neuroendocrinology | ECE2020

To score or not to score? Is Ki-67 analysis worthwhile in pituitary neuroendocrine tumours?

Benjamin Loughrey Paul , Craig Stephanie , Herron Brian , Abdullahi Sidi Fatima , McQuaid Stephen , Kelly Paul , Humphries Matt , Parkes Eileen , McArt Darragh , Hunter Steven , Korbonits Marta , James Jacqueline

Pituitary neuroendocrine tumours (PitNETs) are heterogeneous and have limited biomarkers to predict their behaviour, thus making their prognostication difficult. Ki-67 is a protein expressed in active phases of the cell cycle and is one of the biomarkers utilized in routine assessment of PitNET tissue. Current European Society of Endocrinology recommendations advise that histopathological analysis of PitNETs should as a minimum include Ki-67 proliferation index and anterior pi...

ea0032oc1.1 | Pituitary & Molecular Endocrinology | ECE2013

The consequences of changing endogenous GH/IGF1 levels on carcinogen-induced mammary gland tumorigenesis are dependent on metabolic status in mice

Gahete Manuel D , Cordoba-Chacon Jose , Lantvit Daniel D , Perez-Jiminez Francisco , Lopez-Miranda Jose , Swanson Steven M , Castano Justo P , Luque Raul M , Kineman Rhonda D

ESE Young Investigator AwardIntroduction: GH and IGF1 are thought to promote breast carcinogenesis as circulating levels of GH/IGF1 are positively correlated with breast cancer risk in epidemiologic studies, and mouse models with developmental GH/IGF1 deficiency or resistance are less susceptible to breast cancer development. However, no studies have shown that high levels of circulating GH/IGF1 can promote mammary tumorigenesis. In this...

ea0031p146 | Growth and development | SFEBES2013

Pre-clinical investigation of therapy for segmental overgrowth caused by constitutive activation of phosphoinositide-3 kinas: lessons for cancer therapy

Parker Victoria , Groeneveld Matthijis , Zhang Qifeng , Rudge Simon , Lindhurst Marjorie , Huson Susan , O'Rahilly Steven , Biesecker Leslie , Barroso Ines , Wakelam Michael , Semple Robert

Introduction: We recently reported cases of segmental overgrowth due to mosaic heterozygous activating mutations in the p110α catalytic subunit of PI3K. The index case presented with life-long, massive overgrowth of both legs with a lean upper body. Mobility was threatened by continued growth. mTORC1 inhibition has been effective at slowing excess growth due to loss of PTEN function, a negative regulator of PI3K. We hypothesised that mTORC1 inhibition would also be effect...

ea0022p464 | Female reproduction | ECE2010

Kisspeptin levels in high risk pregnancies related to chronic diseases: insulin dependent diabetes mellitus (IDDM) and arterial hypertension (H)

Miljic Dragana , Cetkovic Aleksandar , Ljubic Aleksandar , Patterson Michael , Ghatei Mohammad , Bloom Steven , Djurovic Marina , Doknic Mirjana , Pekic Sandra , Stojanovic Marko , Popovic Vera

Objective: Kisspeptin is hormone involved in the initiation and maintenance of fertility. Placenta is the major source of kisspeptin but its role during gestation is still matter of debate. Studies investigating kisspeptin levels during gestation in patients with diabetes and hypertension are lacking. Our aim was to prospectively evaluate kisspeptin levels in pregnant women with chronic diseases such as IDDM and H.Design and methods: Kisspeptin levels we...

ea0020s28.1 | Receptor Modulators | ECE2009

Diverse actions of the nuclear receptor corepressor RIP140 in metabolic regulation

Parker Malcolm , Christian Mark , Kiskinis Evangelos , Fritah Asmaa , Poliandri Ariel , Steel Jenny , Hallberg Magnus , Herzog Birger , Seth Asha , Dilworth Steven , White Roger

PGC1 and RIP140 are key regulators of nuclear receptor signalling that control metabolic gene expression in adipose tissue, liver and muscle. PGC1 promotes whereas RIP140 represses the expression of a network of catabolic genes in adipose and muscle. Thus mice devoid of RIP140 accumulate less fat in adipose tissue and liver while mitochondrial biogenesis and respiration is increased in type 2 muscle fibres; as a consequence, the mice maintain their insulin sensitivity as they ...

ea0020p52 | Adrenal | ECE2009

Expression of mTOR pathway in human adrenocortical carcinomas and in vitro effects of mTOR inhibitors in human adrenocortical cell lines

De Martino Maria Cristina , van Koetsveld Peter , Sprij-Mooij Diana , Feelders Richard A , Lamberts Steven W J , de Herder Wouter W , Colao Annamaria , Pivonello Rosario , Hofland Leo J

Background: Adrenocortical carcinoma (ACC) is an uncommon malignancy with a still scantily understood pathogenesis and generally poor prognosis. Surgery, performed at early stages, offers the best chance for cure, but unfortunately, it is often noncurative. Medical treatment produced disappointing responses. mTOR inhibitors, such as sirolimus (S) and temsirolimus (T), are promising antineoplastic drugs in several types of carcinomas.Methods: To evaluate ...

ea0016s24.4 | State of the art in the therapy of pituitary disease | ECE2008

Development of a disease-related QoL-questionnaire for Cushing’s disease

Webb Susan M , Badia Xavier , Barahona Maria-Jose , Colao Annamaria , Strasburger Christian J , Tabarin Antoine , van Aken Maarten , Pivonello Rosario , Stalla Gunther , Lamberts Steven W J , Glusman Joan

Chronic exposure to hypercortisolism significantly impacts on patient’s health and health-related quality of life (HRQoL). We developed a disease-generated questio-nnaire to evaluate HRQoL in Cushing’s syndrome (CS) (CushingQoL); in 125 (104 females) patients recruited in Spain, France, Germany, The Netherlands and Italy, clinical and hormonal data were collected and correlated with results of the generic SF-36 questionnaire, a question on self-perceived general heal...

ea0016p395 | Neuroendocrinology | ECE2008

Dopamine receptor expression and dopamine agonist effectiveness in corticotroph pituitary tumors: comparison with clinical, biochemical radiological and pathological features of patients with Cushing's disease

Pivonello Rosario , de Herder Wouter W , Ferone Diego , Kros Johan M , De Caro Maria Laura Del Basso , Lombardi Gaetano , Colao Annamaria , Hofland Leo J , Lamberts Steven WJ

Dopamine receptors (DR) are expressed in the majority of corticotroph pituitary tumors and the dopamine agonist cabergoline is effective in controlling cortisol hypersecretion in around 50% of patients with Cushing’s disease (CD). In order to characterize the tumors expressing D2 receptors and the profile of patients which might respond to the treatment with D2 agonists, the current study has the aim to correlate D2 receptor expression and...

ea0015oc21 | Tumours, diabetes, bone | SFEBES2008

Delineating the mechanisms of Visfatin regulation in human AT and the implications of TZD treatment in Type 2 Diabetes

McGee Kirsty , Harte Alison , da Silva Nancy , Creely Steven , Baker Adam , Kusminski Christine , Khanolkar Manish , Evans Marc , Chittari Madhu , Patel Vinod , Boardman Shirine , Kumar Sudhesh , McTernan Philip

Objective: The adipocytokine visfatin, expressed in abdominal adipose tissue (AT) is thought to mimic insulin activity. However, whilst central adiposity is closely related to insulin resistance (IR) and T2DM, visfatins’ role in the development of these conditions remains unclear.Method: We investigated circulating visfatin levels in non-diabetic (ND) and diabetic (T2DM) subjects and in T2DM patients pre- and post- rosiglitazone (RSG) treatment. We ...