Efficacy of a dopamine-somatostatin chimeric molecule, BIM-23A760, in the control of cell growth from primary cultures of human non-functioning pituitary adenomas: a multi-center study.

Dopamine D2 and somatostatin receptors (sstrs) were reported to affect non-functioning pituitary adenoma (NFPA) proliferation in vitro. However, the reported results differ according to the experimental conditions used. We established an experimental protocol allowing reproducible evaluation of NFPA cell proliferation in vitro, to test and compare the antiproliferative effects of dopamine and somatostatin analogs (alone or in combination) with the activity of the dopamine-somatostatin chimeric molecule BIM-23A760.

Luteinizing hormone-releasing hormone agonists in the treatment of prostate cancer: a review of their discovery, development, and place in therapy.

Background: Early identification of the biological activity of luteinizing hormone-releasing hormone (LHRH) paved the way for the synthesis of analogues with enhanced potency and biological properties. Early testing in animal models and humans provided insight into the potential clinical uses of these substances, and, within 10 years, LHRH-agonist therapy had become available for use in patients with advanced prostate cancer (PC). Over time, the role of LHRH-agonist therapy has expanded to include use as part of multimodal treatment regimens throughout the course of the disease.

Somatostatin and dopamine receptor expression in lung carcinoma cells and effects of chimeric somatostatin-dopamine molecules on cell proliferation.

To study somatostatin/dopamine (SS/D) synergy in a human cell system constitutively expressing SS and D receptors (SSR and DR, respectively), we characterized the expression of SSR and DR subtypes in the non-small-cell lung cancer line Calu-6, and then we evaluated the effect on cell proliferation of SS/D chimeric molecules (BIM-23A387 and BIM-23A370), which bind with high affinity both sst(2) and D(2)R, and compared the results with those obtained by using SS-14 and subtype-selective SS analogs (SSA) and D agonists (DA). Because Calu-6 cells produce insulin-like growth factor (IGF) and IGF-binding protein (IGFBP) peptides, which play a role in the autocrine/paracrine control of cell growth, we also investigated the effects of chimeric compounds on secretion and expression of IGF system components. Relative high levels of sst(2) and the long isoform of the D(2)R were detected by real-time RT-PCR and Western blot in Calu-6, together with sst(5) and to a lesser extent sst(3) and D(4)R.

Suppression of rat and human growth hormone and prolactin secretion by a novel somatostatin/dopaminergic chimeric ligand.

As cotreatment of somatostatin (SRIF) and dopamine (DA) agonists reduces GH in acromegaly more effectively than either agonist alone, SRIF and DA receptors (SSTR and DAR) may interact with enhanced functional activity. The selective SSTR2 agonist, BIM-23023 (50% effective dose, 0.42), and the DAR2 agonist, BIM-53097 (50% effective dose, 22.