In Vitro Head-to-Head Comparison Between Octreotide and Pasireotide in GH-Secreting Pituitary Adenomas

被引:55
作者
Gatto, Federico [1 ]
Feelders, Richard A. [1 ,2 ]
Franck, Sanne E. [1 ]
van Koetsveld, Peter M. [1 ]
Dogan, Fadime [1 ]
Kros, Johan M. [2 ,3 ]
Neggers, Sebastian J. C. M. M. [1 ,2 ]
van der Lely, Aart-Jan [1 ,2 ]
Lamberts, Steven W. J. [1 ]
Ferone, Diego [4 ]
Hofland, Leo J. [1 ,2 ]
机构
[1] Erasmus Univ, Div Endocrinol, Dept Internal Med, Med Ctr, NL-3000 CA Rotterdam, Netherlands
[2] Erasmus Univ, Pituitary Ctr Rotterdam, Med Ctr, NL-3000 CA Rotterdam, Netherlands
[3] Erasmus Univ, Dept Pathol, Med Ctr, NL-3000 CA Rotterdam, Netherlands
[4] Univ Genoa, Endocrinol Sect, Dept Internal Med & Med Specialties, Ctr Excellence Biomed Res, I-16126 Genoa, Italy
关键词
SOMATOSTATIN RECEPTOR SUBTYPES; GENE-EXPRESSION LEVELS; CORTICOTROPH ADENOMAS; MONOCLONAL-ANTIBODIES; QUANTITATIVE-ANALYSIS; HORMONE-SECRETION; POTENT INHIBITOR; ANALOG SOM230; EFFICACY; THERAPY;
D O I
10.1210/jc.2017-00135
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 sst(2)/sst(5) 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 sst(2) mRNA expression and lower sst(2)/sst(5) 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.
引用
收藏
页码:2009 / 2018
页数:10
相关论文
共 34 条
  • [1] The 2004 World Health Organization classification of pituitary tumors: What is new?
    Al-Shraim, M
    Asa, SL
    [J]. ACTA NEUROPATHOLOGICA, 2006, 111 (01) : 1 - 7
  • [2] SOM230: a novel somatostatin peptidomimetic with broad somatotropin release inhibiting factor (SRIF) receptor binding and a unique antisecretory profile
    Bruns, C
    Lewis, I
    Briner, U
    Meno-Tetang, G
    Weckbecker, G
    [J]. EUROPEAN JOURNAL OF ENDOCRINOLOGY, 2002, 146 (05) : 707 - 716
  • [3] Acromegaly Clinical Trial Methodology Impact on Reported Biochemical Efficacy Rates of Somatostatin Receptor Ligand Treatments: A Meta-Analysis
    Carmichael, John D.
    Bonert, Vivien S.
    Nuno, Miriam
    Ly, Diana
    Melmed, Shlomo
    [J]. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2014, 99 (05) : 1825 - 1833
  • [4] Expression of SSTR2a, but not of SSTRs 1, 3, or 5 in Somatotroph Adenomas Assessed by Monoclonal Antibodies Was Reduced by Octreotide and Correlated With the Acute and Long-Term Effects of Octreotide
    Casar-Borota, Olivera
    Heck, Ansgar
    Schulz, Stefan
    Nesland, Jahn Marthin
    Ramm-Pettersen, Jon
    Lekva, Tove
    Alafuzoff, Irina
    Bollerslev, Jens
    [J]. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2013, 98 (11) : E1730 - E1739
  • [5] Agonist-Biased Signaling at the sst2A Receptor: The Multi-Somatostatin Analogs KE108 and SOM230 Activate and Antagonize Distinct Signaling Pathways
    Cescato, Renzo
    Loesch, Kimberly A.
    Waser, Beatrice
    Maecke, Helmut R.
    Rivier, Jean E.
    Reubi, Jean Claude
    Schonbrunn, Agnes
    [J]. MOLECULAR ENDOCRINOLOGY, 2010, 24 (01) : 240 - 249
  • [6] Expression of somatostatin receptors, SSTR2A and SSTR5, in 108 endocrine pituitary tumors using immunohistochemical detection with new specific monoclonal antibodies
    Chinezu, Laura
    Vasiljevic, Alexandre
    Jouanneau, Emmanuel
    Francois, Patrick
    Borda, Angela
    Trouillas, Jacqueline
    Raverot, Gerald
    [J]. HUMAN PATHOLOGY, 2014, 45 (01) : 71 - 77
  • [7] Pasireotide Versus Octreotide in Acromegaly: A Head-to-Head Superiority Study
    Colao, A.
    Bronstein, M. D.
    Freda, P.
    Gu, F.
    Shen, C. -C.
    Gadelha, M.
    Fleseriu, M.
    van der Lely, A. J.
    Farrall, A. J.
    Resendiz, K. Hermosillo
    Ruffin, M.
    Chen, Y.
    Sheppard, M.
    [J]. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2014, 99 (03) : 791 - 799
  • [8] Resistance to Somatostatin Analogs in Acromegaly
    Colao, Annamaria
    Auriemma, Renata S.
    Lombardi, Gaetano
    Pivonello, Rosario
    [J]. ENDOCRINE REVIEWS, 2011, 32 (02) : 247 - 271
  • [9] Coexpression of Dopamine and Somatostatin Receptor Subtypes in Corticotroph Adenomas
    de Bruin, Christiaan
    Pereira, Alberto M.
    Feelders, Richard A.
    Romijn, Johannes A.
    Roelfsema, Ferdinand
    Sprij-Mooij, Diane M.
    van Aken, Maarten O.
    van der Lelij, Aart-Jan
    de Herder, Wouter W.
    Lamberts, Steven W. J.
    Hofland, Leo J.
    [J]. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2009, 94 (04) : 1118 - 1124
  • [10] Medical Therapy of Acromegaly Efficacy and Safety of Somatostatin Analogues
    Feelders, Richard A.
    Hofland, Leo J.
    van Aken, Maarten O.
    Neggers, Sebastian J.
    Lamberts, Steven W. J.
    de Herder, Wouter W.
    van der Lely, Aart-Jan
    [J]. DRUGS, 2009, 69 (16) : 2207 - 2226