In Vitro Head-to-Head Comparison Between Octreotide and Pasireotide in GH-Secreting Pituitary Adenomas
Autor: | Steven W. J. Lamberts, Sanne E Franck, Diego Ferone, Sebastian J C M M Neggers, Leo J. Hofland, Richard A Feelders, Fadime Dogan, Aart Jan van der Lely, Peter M. van Koetsveld, Federico Gatto, Johan M. Kros |
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Přispěvatelé: | Internal Medicine, Pathology |
Rok vydání: | 2017 |
Předmět: |
Male
0301 basic medicine genetic structures Endocrinology Diabetes and Metabolism Clinical Biochemistry Octreotide Polymerase Chain Reaction Biochemistry chemistry.chemical_compound 0302 clinical medicine Endocrinology Tumor Cells Cultured Receptors Somatostatin Human Growth Hormone Somatostatin receptor Middle Aged Immunohistochemistry Growth hormone secretion Somatostatin Female medicine.drug Adenoma Adult medicine.medical_specialty Adolescent Antineoplastic Agents Hormonal 030209 endocrinology & metabolism Context (language use) In Vitro Techniques Young Adult 03 medical and health sciences Internal medicine Acromegaly medicine Humans RNA Messenger Aged business.industry Biochemistry (medical) medicine.disease eye diseases Pasireotide Prolactin 030104 developmental biology chemistry sense organs Growth Hormone-Secreting Pituitary Adenoma business |
Zdroj: | Journal of Clinical Endocrinology and Metabolism, 102(6), 2009-2018. Endocrine Society |
ISSN: | 1945-7197 0021-972X |
Popis: | Context First-generation somatostatin analogs (SSAs), such as octreotide (OCT), are the first line medical therapy for acromegaly. Pasireotide (PAS), a newly developed SSA, has shown promising results in the treatment of acromegaly. Objective To compare the antisecretory effect of OCT and PAS in primary cultures of growth hormone (GH)-secreting pituitary adenomas (GH-omas). To correlate responses with the adenoma somatostatin receptor (SSTR) profile. Design The effect of OCT and PAS on GH (and PRL) secretion was tested in 33 GH-oma cultures. SSTR expression was evaluated in adenoma samples. Setting and Patients Patients with acromegaly referred to the Erasmus Medical Center (Rotterdam, The Netherlands). Interventions OCT and PAS treatment for 72 hours (10 nM). Main Outcome Measures GH (and PRL) concentrations in cell culture media. SSTR expression in adenoma samples. Results The overall effect of OCT (-36.8%) and PAS (-37.1%) on GH secretion was superimposable. We identified three adenoma groups: PAS+ (PAS more effective than OCT), n = 6; PAS = OCT, n = 22; and OCT+ (OCT more effective than PAS), n = 5. PAS+ adenomas showed lower somatostatin receptor subtype (sst)2 messenger RNA (mRNA) and sst2/sst5 mRNA ratio, compared with the other groups (P < 0.05). PAS inhibited PRL hypersecretion more than OCT (P < 0.01). Conclusions Overall, OCT and PAS equally reduced GH secretion in vitro. Adenomas with lower sst2 mRNA expression and lower sst2/sst5 mRNA ratio were better responders to PAS compared with OCT. SSTR evaluation in GH-omas may become a tool for tailored SSA treatment in acromegaly. |
Databáze: | OpenAIRE |
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