Dissociation between tumor shrinkage and hormonal response during somatostatin analog treatment in an acromegalic patient: Preferential expression of somatostatin receptor subtype 3

Casarini, A; Pinto, Emília M.; Jallad, Raquel S.; Giorgi, Ricardo Rodrigues; Giannella-Neto, Daniel; Bronstein, Marcello D.

doi:10.1007/bf03347378

Cited by 42 publications

(27 citation statements)

References 24 publications

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“…Also, an interesting case report of a patient, which displayed tumor shrinkage, without hormonal control, in response to SA treatment, showed the tumor preferentially expressed SSTR3 (37). This isolated case suggests that SSTR3 can confer apoptotic activity in pituitary tumor tissue.…”

Section: Discussionmentioning

confidence: 84%

Quantitative analysis of somatostatin receptor subtypes (1–5) gene expression levels in somatotropinomas and correlation to in vivo hormonal and tumor volume responses to treatment with octreotide LAR

Taboada

Luque

Neto

et al. 2008

European Journal of Endocrinology

163

110

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Objective: To determine whether the somatostatin receptor subtype (SSTR) expression profile correlates with hormonal and tumor volume responses to postsurgical octreotide long acting repeatable (OCT LAR) treatment. Design and methods: Quantitative real-time RT-PCR was used to evaluate the absolute mRNA copy numbers for all five SSTR subtypes in 22 somatotropinomas. Response to OCT LAR was studied by hormone levels (GH and IGF-I) and tumor volume (sella turcica magnetic resonance imaging). Results: SSTR5 was present at the highest level followed by SSTR2, SSTR3, SSTR1, and SSTR4 (2327 (1046-5555), 2098, 97 (0-460), 14 (0-29 480), and 0 (0-652) copies respectively). Positive correlations were found between SSTR2 levels and the percentage decrease of GH and IGF-I after 3 (rZ0.49, P!0.027 and rZ0.49, P!0.029 respectively) and 6 (rZ0.59, P!0.006 and rZ0.58, P!0.008 respectively) months of OCT LAR. A negative correlation was found between SSTR5 mRNA levels and the percentage decrease of GH after 3 months of OCT LAR (rZK0.52, PZ0.016, nZ21). A higher SSTR2/SSTR5 ratio was observed among patients who obtained hormonal control with OCT LAR, when compared with those uncontrolled (2.4 (0.7-10) vs 0.3 (0.1-7.7), PZ0.001). A ROC curve analysis showed a SSTR2/SSTR5 ratio of 1.3 as the best predictor of disease control, with a sensitivity of 88% and a specificity of 92% -area under curve, 0.9. A positive correlation was also found between SSTR2 mRNA levels and the percentage decrease in tumor volume after 6 months of OCT LAR (rZ0.79, PZ0.002, nZ12). Conclusions: Somatostatin receptor subtype 2 mRNA expression levels in somatotropinomas correlate positively with in vivo hormonal and tumor volume responses to OCT LAR. European Journal of Endocrinology 158 295-303

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Section: Discussionmentioning

confidence: 84%

Quantitative analysis of somatostatin receptor subtypes (1–5) gene expression levels in somatotropinomas and correlation to in vivo hormonal and tumor volume responses to treatment with octreotide LAR

Taboada

Luque

Neto

et al. 2008

European Journal of Endocrinology

163

110

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“…Finally, lanreotide was also shown to have lower affinity for the subtype 3 of somatostatin receptor than octreotide, although the overall binding for both molecules is modest [16]. It is noteworthy that both subtype 3 and 5 of somatostatin receptor were shown to play important roles in mediating the shrinkage effects of SSA, either inhibiting cell proliferation or activating cell apoptosis [12,13,16,39,40]. In this light, the different affinity profiles between octreotide and lanreotide may lead to different shrinkage effects of these drugs on GH-secreting adenomas.…”

Section: Discussionmentioning

confidence: 95%

“…Therefore, the evaluation of tumor shrinkage may be important in acromegalic patients defined as resistant to SSA on the basis of biochemical evaluation [9]. In these patients, SSA may maintain some effect on tumor mass which could be important for the choice of the subsequent therapeutic approach [9,[11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Effects of lanreotide SR and Autogel on tumor mass in patients with acromegaly: a systematic review

Mazziotti,

Giustina

2009

Pituitary

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Long-acting somatostatin analogs (SSA) are widely used for the treatment of acromegaly achieving biochemical control of the disease in 50-75% of the patients. One of the goals of the treatment of acromegaly is the control of tumor growth, especially in patients in whom SSAs are used as first-line therapy. Over the recent years, there has been growing evidence that SSAs are able to induce tumor shrinkage in patients with acromegaly. However, most of the data are from patients under treatment with octreotide, either subcutaneously or intramuscularly with long-acting formulation, whereas the data on lanreotide SR or Autogel are very few. Indeed, octreotide and lanreotide, i.e. the two commercially available SSAs, show slight differences in pharmacokinetics and patterns of receptor affinities with potentially different therapeutic effects. We aimed to perform a systematic review of literature data concerning the shrinkage effects of long-acting lanreotide in patients with acromegaly. The analysis was focused on the following issues: differences in shrinkage effects between primary and secondary medical treatment, predictive value of baseline tumor volume and correlation between biochemical control and shrinkage effects. The peer-reviewed medical literature was searched to identify clinical trials studying the effects of lanreotide SR or Autogel on adenoma size in acromegaly. To be included in this analysis, studies had one of the following designs: randomized controlled trial; prospective, nonrandomized trial; retrospective study. Twenty-two studies were found to be eligible for the final analysis, in which tumor size was measured as an end-point for lanreotide treatment. Overall a total of 32.8% of patients experienced a variable degree (from 10 to 77%) of tumor shrinkage during lanreotide SR or Autogel treatment. The analysis showed that tumor shrinkage was more frequent in naïve patients as compared with those previously treated by radiotherapy, surgery or drugs other than lanreotide. The data on the correlation between tumor shrinkage and baseline tumor size were discordant, but when baseline tumor size was specified, more than 80% of patients undergoing shrinkage under lanreotide Autogel had macroadenomas. Finally, with lanreotide Autogel there was no evident correlation between biochemical response and tumor shrinkage. Our systematic review of the literature shows that lanreotide particularly when used as first-line therapy is able to quite frequently induce tumor shrinkage in patients with acromegaly. This finding suggests that this drug may have a role in the primary treatment of acromegaly.

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“…Somatostatin analog-resistant acromegalic patients may present tumor shrinkage without hormonal normalization, the former being related to a high expression of either sst5 or sst3. (Resmini et al, 2007;Casarini et al, 2006). In nonfunctioning pituitary adenomas primary cultures, sst2-selective agonists inhibit hormone secretion without affecting cell proliferation, whereas an sst1-selective agonist inhibits secretory activity and cell viability and sst5-selective agonists promote cell viability (Zatelli et al, 2004).…”

Section: Antitumor Actions Of Somatostatin Analogsmentioning

confidence: 99%

Antitumor effects of somatostatin

Pyronnet

Bousquet

Najib

et al. 2008

Molecular and Cellular Endocrinology

160

118

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SummarySince its discovery three decades ago as an inhibitor of GH release from the pituitary gland, somatostatin has attracted much attention because of its functional role in the regulation of a wide variety of physiological functions in the brain, pituitary, pancreas, gastrointestinal tract, adrenals, thyroid, kidney and immune system. In addition to its negative role in the control of endocrine and exocrine secretions, somatostatin and analogs also exert inhibitory effects on the proliferation and survival of normal and tumor cells. Over the past 15 years, studies have begun to reveal some of the molecular mechanisms underlying the antitumor activity of somatostatin. This review covers the present knowledge in the antitumor effect of somatostatin and analogs and discusses the perspectives of novel clinical strategies based on somatostatin receptor sst2 gene transfer therapy.

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Dissociation between tumor shrinkage and hormonal response during somatostatin analog treatment in an acromegalic patient: Preferential expression of somatostatin receptor subtype 3

Abstract: These unusual clinical and receptor subtypes profile suggest an important role of SSTR3 on tumor shrinkage. The low affinity of LAN and OCT for this SSTR subtype could be compensated by its high expression in this GH-secreting pituitary macroadenoma.

Cited by 42 publications

References 24 publications

Quantitative analysis of somatostatin receptor subtypes (1–5) gene expression levels in somatotropinomas and correlation to in vivo hormonal and tumor volume responses to treatment with octreotide LAR

Quantitative analysis of somatostatin receptor subtypes (1–5) gene expression levels in somatotropinomas and correlation to in vivo hormonal and tumor volume responses to treatment with octreotide LAR

Effects of lanreotide SR and Autogel on tumor mass in patients with acromegaly: a systematic review

Antitumor effects of somatostatin

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