<i>In vivo</i> secretory potential and the effect of combination therapy with octreotide and cabergoline in patients with clinically non‐functioning pituitary adenomas

Andersen, Marianne; Bjerre, Per; Schrøder, Henrik Daa; Edal, A.; Høilund-Carlsen, Poul Fl.; Pedersen, Per Hyltoft; Hagen, Claus

doi:10.1046/j.1365-2265.2001.01172.x

Cited by 61 publications

(29 citation statements)

References 30 publications

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“…These data would indicate a stimulatory role for SSTR5 in NFA cell proliferation, suggesting that the use of compounds selectively interacting with SSTR5 in NFA medical therapy might be counterproductive. In addition, this effect might account for the lack of volume reduction (Colao et al 2000, Andersen et al 2001 or the increase in tumor volume (Gasperi et al 1993) observed in NFA patients treated with octreotide or lanreotide, which mainly interacts with SSTR2 and SSTR5. However, this does not seem to be a general mechanism in pituitary adenomas, because previous evidence from somatotroph and corticotroph pituitary tumors suggests that the additional activation of SSTR5 might be responsible for the enhanced efficacy of SRIF analogs in reducing both secretion and cell proliferation (Shimon et al 1997, Hofland et al 2005.…”

Section: Discussionmentioning

confidence: 99%

Pasireotide, a multiple somatostatin receptor subtypes ligand, reduces cell viability in non-functioning pituitary adenomas by inhibiting vascular endothelial growth factor secretion

Zatelli¹,

Piccin²,

Tagliati³

et al. 2007

Endocr Relat Cancer

108

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Section: Discussionmentioning

confidence: 99%

Pasireotide, a multiple somatostatin receptor subtypes ligand, reduces cell viability in non-functioning pituitary adenomas by inhibiting vascular endothelial growth factor secretion

Zatelli¹,

Piccin²,

Tagliati³

et al. 2007

Endocr Relat Cancer

108

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“…Page 6, paragraph 1, line 14: the paragraph "This effect might explain the lack of efficacy of medical treatment by means of octreotide or Lan, compounds mainly interacting with SSTR2 and less with SSTR5, in some NFA (Oppizzi et al 1998, Andersen et al 2001, Colao et al 2000, Gasperi et al 1993. Moreover, our findings might provide a possible explanation for the increase in tumor volume rarely observed during such therapy (Andersen et al 2001). These results suggest that indication for medical therapy with octreotide or Lan in NFA patients with SSTR5 expressing tumors should be critically discussed until clinical evidence for beneficial effects has clearly been demonstrated."…”

Section: Physiol 94 205-210mentioning

confidence: 99%

“…On the contrary, our data show that the SSTR2 selective agonist did not influence NFA cell viability, which was promoted by the SSTR5 selective agonist. This effect might explain the lack of efficacy of medical treatment by means of octreotide or Lan, compounds mainly interacting with SSTR2 and less with SSTR5, in some NFA (Oppizzi et al 1998, Andersen et al 2001, Colao et al 2000, Gasperi et al 1993. Moreover, our findings might provide a possible …”

mentioning

confidence: 99%

In vitro testing of new somatostatin analogs on pituitary tumor cells

Zatelli

Ambrosio

Bondanelli

et al. 2008

Molecular and Cellular Endocrinology

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It has been indeed demonstrated that native SRIF inhibits secretion and proliferation of both normal and neoplasic pituitary cells by inducing several intracellular pathways, depending on receptor subtype and target tissue (Ferjoux et al. 2000). Therefore, many studies subsequently explored SSTR subtype expression in pituitary adenomas, demonstrating that SSTR2 is the most frequently expressed subtype (Panetta and Patel, 1995 A c c e p t e d M a n u s c r i p t 3 SSTR 2 and 5 mRNA were always expressed, while SSTR1 and 3 mRNA were expressed in 11 and 12 tumors, respectively. Primary cultures deriving from these tumors were tested with 1 M SRIF or lanreotide (Lan), a SRIF analog preferentially binding with high affinity SSTR2 and less affinity SSTR5, or with SSTR2-and SSTR5-selective analogs. After 24 hours no effect was observed in some cultures, but in others (as well as in the GH3 rat cell line) a parallel reduction in cell viability and DNA synthesis was observed. This study also highlighted a dissociation between the in vitro effects of SRIF analogs on tumor cell proliferation and on GH secretion. In nearly 60% of the tumors, treatment with SRIF, Lan, SSTR2-or SSTR5-selective agonists significantly inhibited GH secretion.by a median of 33%. However, not all these primary cultures responded to SRIF and its analogs in terms of cell viability reduction, suggesting that inhibition of cell proliferation occurs independently of the effects on GH secretion (Danila et al. 2001). Similarly, an important tumor shrinkage has been described in an acromegalic patient during primary therapy with SRIF analogs, in the absence of hormonal normalization . In this case, the lack of antisecretory action of octreotide, a SRIF analog preferentially binding with high affinity SSTR2 and less affinity SSTR5, was in keeping with the absence of SSTR2 and SSTR5 expression by the tumor, which expressed almost exclusively SSTR3. The latter SSTR subtype has been indeed demonstrated to transduce important antiproliferative signals, since its activation causes apoptosis in heterlogous expression systems (Sharma et al. 1996). Further support to the hypothesis that antiproliferative effects are independent of antisecretory actions of SRIF analogs is provided by a recent report, describing the case of an acromegalic patient displaying dramatic tumor shrinkage during primary therapy with octreotide, without hormonal normalization. Again, in vitro SRIF and its analogs at 10 nM induced a scant antisecretory effect, but potently inhibited thymidine incorporation. This effect was evident for compounds interacting with SSTR5, in keeping with the finding that SSTR5 expression levels were greater than SSTR2 in the tissue (Resmini et al. 2007). In light of the recent discoveries concerning SSTR biology, we attempted to clarify the possible functional interaction between SSTR and dopamine (DA) receptor subtype 2 (DR2). To this aim, we investigated DR2 and SSTR2 and 5 expression in 25 GH-secreting pituitary adenomas, which were tested in primary culture...

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“…As already mentioned, a functional interaction between D 2 and sst 5 receptors has recently been reported (15), supporting a potential benefit from combined use of these two categories of compounds. In a recent study, the effect of combination therapy with octreotide and cabergoline was investigated in ten patients with NFA (55). Tumour shrinkage O10% has been reported in six out of ten patients.…”

Section: Non-functioning Pituitary Adenomasmentioning

confidence: 99%

Combined therapy of somatostatin analogues and dopamine agonists in the treatment of pituitary tumours

Colao

Filippella²,

Pivonello

et al. 2007

eur j endocrinol

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Pituitary tumours express both somatostatin and dopamine receptors. Medical treatment with somatostatin analogues is a cornerstone of GH-and TSH-secreting tumours, while treatment with dopamine agonists is a cornerstone of prolactin-secreting tumours. Dopamine agonists have also demonstrated some efficacy in patients with GH-and TSH-secreting adenomas. Neither ACTHsecreting nor clinically non-functioning tumours have a well-established medical treatment. Nevertheless, some recent results have indicated a potential usefulness of the dopamine agonist cabergoline in patients with pituitary-dependent Cushing's disease. Combination treatment with both somatostatin analogues and dopamine agonists has been poorly investigated. Some studies conducted in small series have documented an additive effect of both drugs in patients with GH-secreting adenomas. Of mention is that none of the studies were randomised and cross-sectional so that the results should be confirmed by other well-designed studies. No data are available in other pituitary tumour histotypes. Preliminary observations in patients with clinically non-functioning adenomas are very promising.

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In vivo secretory potential and the effect of combination therapy with octreotide and cabergoline in patients with clinically non‐functioning pituitary adenomas

Cited by 61 publications

References 30 publications

Pasireotide, a multiple somatostatin receptor subtypes ligand, reduces cell viability in non-functioning pituitary adenomas by inhibiting vascular endothelial growth factor secretion

Pasireotide, a multiple somatostatin receptor subtypes ligand, reduces cell viability in non-functioning pituitary adenomas by inhibiting vascular endothelial growth factor secretion

In vitro testing of new somatostatin analogs on pituitary tumor cells

Combined therapy of somatostatin analogues and dopamine agonists in the treatment of pituitary tumours

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