Dataset Information

Expression analysis of dopamine receptor subtypes in normal human pituitaries, nonfunctioning pituitary adenomas and somatotropinomas, and the association between dopamine and somatostatin receptors with clinical response to octreotide-LAR in acromegaly.

ABSTRACT:

Context

Dopamine receptor (DR) and somatostatin receptor subtype expression in pituitary adenomas may predict the response to postsurgical therapies.

Objectives

Our objectives were to assess and compare the mRNA levels of DR1-5 and somatostatin receptors 1-5 in normal pituitaries (NPs), nonfunctioning pituitary adenomas (NFPAs), and somatotropinomas. In addition, we determined whether the level of DR expression correlates with the in vivo response to octreotide-LAR in acromegalic patients.

Design and patients

Eight NPs, 30 NFPAs, and 39 somatotropinomas were analyzed for receptor mRNA levels by real-time RT-PCR. The DR2 short variant was estimated as the DR2 long/DR2 total (DR2T). The relationship between DR expression and the postsurgical response to octreotide-LAR was assessed in 19 of the acromegalic patients.

Results

DR3 was not detected. The relationship between expression levels of DR subtypes in NPs and somatotropinomas was DR2T>>>DR4>>DR5>DR1, whereas in NFPAs, DR2T>>>DR4>>DR1>DR5. The DR2 short variant was the predominant DR2 variant in the majority of samples. In acromegalics treated with octreotide-LAR, DR1 was negatively correlated with percent GH reduction (3 months: r = -0.67, P = 0.002; and 6 months: r = -0.58, P = 0.009), and DR5 was positively correlated with percent IGF-I reduction (3 months: r = 0.55, P = 0.01; and 6 months: r = 0.47, P = 0.04).

Conclusions

DR2 is the predominant DR subtype in NPs, NFPAs, and somatotropinomas. The fact that DR1, DR4, and DR5 are also expressed in many adenomas tested suggests that these receptors might also play a role in the therapeutic impact of postsurgical medical therapies in patients with NFPA and acromegaly. This was supported by the finding that the in vivo response to octreotide-LAR was negatively associated with DR1 and positively associated with DR5.

SUBMITTER: Neto LV

PROVIDER: S-EPMC2730344 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature

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Publications

Expression analysis of dopamine receptor subtypes in normal human pituitaries, nonfunctioning pituitary adenomas and somatotropinomas, and the association between dopamine and somatostatin receptors with clinical response to octreotide-LAR in acromegaly.

Neto Leonardo Vieira LV Machado Evelyn de O Ede O Luque Raul M RM Taboada Giselle F GF Marcondes Jorge B JB Chimelli Leila M C LM Quintella Leonardo Pereira LP Niemeyer Paulo P de Carvalho Denise P DP Kineman Rhonda D RD Gadelha Mônica R MR

The Journal of clinical endocrinology and metabolism 20090317 6

<h4>Context</h4>Dopamine receptor (DR) and somatostatin receptor subtype expression in pituitary adenomas may predict the response to postsurgical therapies.<h4>Objectives</h4>Our objectives were to assess and compare the mRNA levels of DR1-5 and somatostatin receptors 1-5 in normal pituitaries (NPs), nonfunctioning pituitary adenomas (NFPAs), and somatotropinomas. In addition, we determined whether the level of DR expression correlates with the in vivo response to octreotide-LAR in acromegalic ...[more]

PMID: 19293270

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Project description:BACKGROUND:Antitumor activity of the combination of somatostatin analogues (SSAs) and the mammalian target of rapamycin (mTOR) inhibitor everolimus in patients with neuroendocrine tumors (NETs) has been reported but not confirmed in prospective trials. MATERIALS AND METHODS:This prospective, multicenter, single-arm phase II EVERLAR study evaluated everolimus 10 mg/day and the SSA octreotide 30 mg every 28 days in patients with advanced nonfunctioning well-differentiated gastrointestinal NETs (GI-NETs) that progressed in the last 12 months (ClinicalTrials.gov NCT01567488). Prior treatment with SSAs and any systemic or locoregional therapy was allowed except for mTOR inhibitors. Patients continued treatment until disease progression or unacceptable adverse events (AEs). The primary endpoint was progression-free survival (PFS) at 12 months; secondary endpoints included early biochemical response, objective response rate (ORR) by RECIST v1.0, overall survival (OS), AEs, activation of mTOR pathway (insulin-like growth factor 1 receptor [IGF1R] and phosphoS6 [pS6] expression). RESULTS:Forty-three patients were included in the intent-to-treat analyses. After 12 months of treatment, 62.3% (95% confidence interval [CI] 48%-77%) of patients had not progressed or died. The 24-month PFS rate was 43.6% (95% CI 29%-58%). The confirmed ORR was 2.3%, and stable disease was 58.1%. Median OS was not reached after 24 months of median follow-up. Dose reductions and temporary interruptions due to AEs were required in 14 (33%) and 33 (77%) patients, respectively. The most frequent AEs were diarrhea, asthenia, mucositis, rash, and hyperglycemia. No correlation was observed between IGFR1 and pS6 expression and PFS/OS. CONCLUSION:The everolimus-octreotide combination provided clinically relevant efficacy in nonfunctioning GI-NETs, similar to the results of RADIANT-2 in functioning setting. IMPLICATIONS FOR PRACTICE:The EVERLAR study reports prospective data of somatostatin analogue in combination with everolimus in nonfunctioning gastrointestinal neuroendocrine tumors suggesting meaningful activity and favorable toxicity profile that supports drug combination in this setting.

Dataset Information

Expression analysis of dopamine receptor subtypes in normal human pituitaries, nonfunctioning pituitary adenomas and somatotropinomas, and the association between dopamine and somatostatin receptors with clinical response to octreotide-LAR in acromegaly.

Context

Objectives

Design and patients

Results

Conclusions

Publications

Expression analysis of dopamine receptor subtypes in normal human pituitaries, nonfunctioning pituitary adenomas and somatotropinomas, and the association between dopamine and somatostatin receptors with clinical response to octreotide-LAR in acromegaly.

Similar Datasets

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