Rapid pituitary tumor shrinkage with dissociation between antiproliferative and antisecretory effects of a long-acting octreotide in an acromegalic patient.
| Autor: | Resmini E; Department of Endocrinology and Metabolism, University of Genova, Viale Benedetto XV 6, 16132 Genoa, Italy., Dadati P, Ravetti JL, Zona G, Spaziante R, Saveanu A, Jaquet P, Culler MD, Bianchi F, Rebora A, Minuto F, Ferone D |
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| Jazyk: | angličtina |
| Zdroj: | The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 2007 May; Vol. 92 (5), pp. 1592-9. Date of Electronic Publication: 2007 Feb 20. |
| DOI: | 10.1210/jc.2006-2084 |
| Abstrakt: | Context: Criteria to define the response to somatostatin (SS) analogs (SSA) in acromegaly are based on biochemical control of the disease. However, the mechanisms of action of SSAs in inhibiting tumor growth and hormonal secretion are only partially understood, and the two effects may occur independently. Objective: The objective of the study was to investigate the dissociation between antiproliferative and antisecretive effects of SSA in an octreotide-resistant patient displaying dramatic tumor shrinkage during primary therapy with octreotide LAR. Design and Setting: We characterized somatostatin and dopamine D(2) receptor expression by immunohistochemistry and real-time RT-PCR. The effects of different receptor-selective, bispecific analogs, and chimeric somatostatin/dopamine compounds on GH secretion and cell proliferation in primary cell cultures of the tumor were assessed. Results: The expression of SS receptor subtypes (sst)(5) and D(2) receptor was higher, compared with the other receptor subtypes. GH inhibition by SS-14 and the two chimeric somatostatin/dopamine compounds was scant but greater than subtype-selective and sst(2)/sst(5) bispecific agonists. Conversely, cell growth was potently inhibited by all test substances. However, SS-14, sst(2)/sst(5) bispecific agonist, and chimeric molecules were more potent than the other compounds. Conclusions: The significant antiproliferative effect of octreotide seems to be related to the higher expression of sst(5) and the negligible antihormonal effect to the lower expression of sst(2). However, activation of multiple receptors by new analogs may produce better control of tumor cell activities. The dissociation between antisecretive and antiproliferative effects observed in vivo and in vitro confirms that SSAs may induce tumor shrinkage despite the lack of effect on GH secretion. |
| Databáze: | MEDLINE |
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