title: Rapid pituitary tumor shrinkage with dissociation between antiproliferative and antisecretory effects of a long-acting octreotide in an acromegalic patient.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
authors.affiliation: Department of Endocrinology and Metabolism, University of Genova, Viale Benedetto XV 6, 16132 Genoa, Italy.
authors.forename: Eugenia
authors.initials: E
authors.lastname: Resmini
authors.forename: Patrizia
authors.initials: P
authors.lastname: Dadati
authors.forename: Jean-Luis
authors.initials: JL
authors.lastname: Ravetti
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Zona
authors.forename: Renato
authors.initials: R
authors.lastname: Spaziante
authors.forename: Alexandru
authors.initials: A
authors.lastname: Saveanu
authors.forename: Philippe
authors.initials: P
authors.lastname: Jaquet
authors.forename: Michael D
authors.initials: MD
authors.lastname: Culler
authors.forename: Federico
authors.initials: F
authors.lastname: Bianchi
authors.forename: Alberto
authors.initials: A
authors.lastname: Rebora
authors.forename: Francesco
authors.initials: F
authors.lastname: Minuto
authors.forename: Diego
authors.initials: D
authors.lastname: Ferone
mesh_terms: D000172:Acromegaly / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000239:Adenoma, Acidophil / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000077465:Cabergoline; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003692:Delayed-Action Preparations; D004873:Ergolines / Q000627:therapeutic use; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D008854:Microscopy, Electron; D015282:Octreotide / Q000008:administration & dosage / Q000627:therapeutic use*; D010911:Pituitary Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013004:Somatostatin / Q000235:genetics; D013936:Thymidine / Q000378:metabolism
chemical_list: D003692:Delayed-Action Preparations; D004873:Ergolines; D012333:RNA, Messenger; D019382:Human Growth Hormone; D013004:Somatostatin; D007334:Insulin-Like Growth Factor I; D000077465:Cabergoline; D015282:Octreotide; D013936:Thymidine