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Featured researches published by Eivind Carlsen.


The Journal of Clinical Endocrinology and Metabolism | 2012

Somatostatin analogs modulate AIP in somatotroph adenomas: the role of the ZAC1 pathway.

Harvinder S. Chahal; Giampaolo Trivellin; Chrysanthia Leontiou; Neda Alband; Robert C. Fowkes; Asil Tahir; Susana Igreja; J. Paul Chapple; Susan Jordan; Amelie Lupp; Stefan Schulz; Olaf Ansorge; Niki Karavitaki; Eivind Carlsen; John Wass; Ashley B. Grossman; Márta Korbonits

CONTEXT Somatotroph adenomas harboring aryl hydrocarbon receptor interacting protein (AIP) mutations respond less well to somatostatin analogs, suggesting that the effects of somatostatin analogs may be mediated by AIP. OBJECTIVE The objective of the investigation was to study the involvement of AIP in the mechanism of effect of somatostatin analogs. DESIGN In the human study, a 16-wk somatostatin analog pretreatment compared with no pretreatment. In the in vitro cell line study, the effect of somatostatin analog treatment or small interfering RNA (siRNA)/plasmid transfection were studied. SETTING The study was conducted at a university hospital. PATIENTS Thirty-nine sporadic and 10 familial acromegaly patients participated in the study. INTERVENTION Interventions included preoperative lanreotide treatment and pituitary surgery. OUTCOME For the human study, GH and IGF-I levels, AIP, and somatostatin receptor staining were measured. For the cell line, AIP and ZAC1 (zinc finger regulator of apoptosis and cell cycle arrest) expression, metabolic activity, and clone formation were measured. RESULTS Lanreotide pretreatment reduced GH and IGF-I levels and tumor volume (all P < 0.0001). AIP immunostaining was stronger in the lanreotide-pretreated group vs. the surgery-only group (P < 0.001). After lanreotide pretreatment, the AIP score correlated to IGF-I changes in females (R = 0.68, P < 0.05). Somatostatin receptor staining was not reduced in samples with AIP mutations. In GH3 cells, 1 nm octreotide increased AIP mRNA and protein (both P < 0.01) and ZAC1 mRNA expression (P < 0.05). Overexpression of wild-type (but not mutant) AIP increased ZAC1 mRNA expression, whereas AIP siRNA knockdown reduced ZAC1 mRNA (both P < 0.05). The siRNA-mediated knockdown of AIP led to an increased metabolic activity and clonogenic ability of GH3 cells compared with cells transfected with a nontargeting control (both P < 0.001). CONCLUSION These results suggest that AIP may play a role in the mechanism of action of somatostatin analogs via ZAC1 in sporadic somatotroph tumors and may explain their lack of effectiveness in patients with AIP mutations.


European Journal of Endocrinology | 2016

Factors predicting pasireotide responsiveness in somatotroph pituitary adenomas resistant to first generation somatostatin analogues: an immunohistochemical study

Donato Iacovazzo; Eivind Carlsen; Francesca Lugli; Sabrina Chiloiro; Serena Piacentini; Antonio Bianchi; Antonella Giampietro; Marilda Mormando; Andrew Clear; Francesco Doglietto; C. Anile; Giulio Maira; Libero Lauriola; G. Rindi; Federico Roncaroli; A. Pontecorvi; Márta Korbonits; Laura De Marinis

AIM To gather data regarding factors predicting responsiveness to pasireotide in acromegaly. PATIENTS AND METHODS SSTR2a, SSTR3, SSTR5, AIP, Ki-67 and the adenoma subtype were evaluated in somatotroph adenomas from 39 patients treated post-operatively with somatostatin analogues (SSAs). A standardized SSTR scoring system was applied (scores 0-3). All patients received first-generation SSAs, and 11 resistant patients were subsequently treated with pasireotide LAR. RESULTS None of the patients with negative or cytoplasmic-only SSTR2a expression (scores 0-1) were responsive to first-generation SSAs, as opposed to 20% (score 2) and 50% of patients with a score of 3 (P=0.04). None of the patients with an SSTR5 score of 0-1 were responsive to pasireotide, as opposed to 5/7 cases with a score of 2 or 3 (P=0.02). SSTR3 expression did not influence first-generation SSAs or pasireotide responsiveness. Tumours with low AIP were resistant to first-generation SSAs (100 vs 60%; P=0.02), while they had similar responsiveness to pasireotide compared to tumours with conserved AIP expression (50 vs 40%; P=0.74). Tumours with low AIP displayed reduced SSTR2 (SSTR2a scores 0-1 44.4 vs 6.7%; P=0.006) while no difference was seen in SSTR5 (SSTR5 scores 0-1 33.3 vs 23.3%; P=0.55). Sparsely granulated adenomas responded better to pasireotide compared to densely granulated ones (80 vs 16.7%; P=0.04). CONCLUSION The expression of SSTR5 might predict responsiveness to pasireotide in acromegaly. AIP deficient and sparsely granulated adenomas may benefit from pasireotide treatment. These results need to be confirmed in larger series of pasireotide-treated patients.


Hormone Research in Paediatrics | 2009

Recent clinical and pathophysiological advances in non-functioning pituitary adenomas.

Márta Korbonits; Eivind Carlsen

Pituitary adenomas are being recognized and diagnosed with increasing frequency. One of the most common forms of pituitary lesion is the clinically non-functioning pituitary adenoma (NFPA), which is often diagnosed incidentally. The vast majority of pituitary adenomas are sporadic, but familial adenomas can occur in the multiple pituitary adenoma type 1 syndrome, in Carney complex or in familial isolated pituitary adenoma. Distinguishing NFPA from prolactinomas can occasionally cause a differential diagnostic problem due to the ‘stalk effect’. NFPA often show hormone synthesis on tissue immunostaining without causing clinical symptoms. Most often these are silent gonadotroph adenomas, with silent corticotroph or somatotroph adenomas occurring less frequently. It is unclear why these silent adenomas do not release hormones at a clinically recognizable level, although it is probable that there is a continuum between fully functional and completely silent adenomas. Another intriguing feature of NFPAs is the lack of clinical response to somatostatin analogues, despite the presence of somatostatin receptors and an often good response in the in vitro setting. Temozolomide has been successfully used for the treatment of a few aggressive pituitary adenomas, and the response to this drug could be influenced by the expression of the DNA repair enzyme O-6-methylguanine DNA methyltransferase. The early diagnosis, prediction of long-term outcome and treatment of NFPAs remain a challenge for endocrinologists.


European Journal of Clinical Investigation | 2013

ACTH-secreting Crooke cell carcinoma of the pituitary

Gábor L. Kovács; Miklós Góth; Fabio Rotondo; Bernd W. Scheithauer; Eivind Carlsen; Ali Saadia; Erika Hubina; László Kovács; István Szabolcs; Pál Nagy; Sándor Czirják; Zoltán Hanzély; Kalman Kovacs; Eva Horvath; Márta Korbonits

Eur J Clin Invest 2012


11th European Congress of Endocrinology | 2009

AIP immunostaining is increased with lanreotide therapy in individuals with acromegaly and predicts changes in IGF-1 levels in female patients

Harvinder S. Chahal; Olaf Ansorge; Niki Karavitaki; Eivind Carlsen; John Wass; Ashley Grossman; Márta Korbonits


Society for Endocrinology BES 2017 | 2017

A comprehensive analysis of the AIP mutation positive pituitary tumour microenvironment: role of stromal cells and the pro-inflammatory cytokine network

Sayka Barry; Antonia Solomou; L Vignola; David M Collier; Eivind Carlsen; Emanuela Gadaleta; Daniel M. Berney; Claude Chelala; Tatjana Crnogorac-Jurcevic; Carles Gaston-Massuet; Marta Korbonits


Society for Endocrinology BES 2016 | 2016

The role of the microenvironment in the invasive phenotype of familial pituitary tumours

Sayka Barry; Eivind Carlsen; Emanuela Gadaleta; Daniel M. Berney; Claude Chelala; Tatjana Crnogorac-Jurcevic; Marta Korbonits


Society for Endocrinology BES 2015 | 2015

Potential molecular mechanism of AIP-mediated cellular invasion

Sayka Barry; Eivind Carlsen; Jumana Saleh; Emanuela Gadaleta; Claude Chelala; Marta Korbonits


Archive | 2015

generation somatostatin analogues: an immunohistochemical study

Donato Iacovazzo; Eivind Carlsen; Francesca Lugli; Sabrina Chiloiro; Serena Piacentini; Antonella Giampietro; Marilda Mormando; Andrew Clear; Francesco Doglietto; Giulio Maira; Libero Lauriola; Guido Rindi; Federico Roncaroli; Alfredo Pontecorvi; Márta Korbonits; Laura De Marinis


Hormone Research in Paediatrics | 2011

Somatostatin Analogue Treatment Increases AIP Protein Expression in Somatotroph Tumours from Patients with Acromegaly and in GH3 Cells in vitro

Harvinder S. Chahal; Olaf Ansorge; Niki Karavitaki; Chrysanthia Leontiou; Eivind Carlsen; John Wass; Ashley B. Grossman; Márta Korbonits

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Márta Korbonits

Queen Mary University of London

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Harvinder S. Chahal

Queen Mary University of London

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Niki Karavitaki

Queen Mary University of London

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Olaf Ansorge

Queen Mary University of London

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Claude Chelala

Queen Mary University of London

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Emanuela Gadaleta

Queen Mary University of London

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Marta Korbonits

Tavistock and Portman NHS Foundation Trust

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Sayka Barry

Queen Mary University of London

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Andrew Clear

Queen Mary University of London

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