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However, information on direct <jats:italic>in vitro<\/jats:italic> effects of BIM-23A760 in normal and tumoral pituitaries remains incomplete. The objective of this study was to analyze BIM-23A760 effects on functional parameters (Ca<jats:sup>2+<\/jats:sup> signaling, hormone expression\/secretion, cell viability and apoptosis) in pituitary adenomas (n\u2009=\u200974), and to compare with the responses of normal primate and human pituitaries (n\u2009=\u20093\u20135). Primate and human normal pituitaries exhibited similar sst2\/sst5\/D2 expression patterns, wherein BIM-23A760 inhibited the expression\/secretion of several pituitary hormones (specially GH\/PRL), which was accompanied by increased sst2\/sst5\/D2 expression in primates and decreased Ca<jats:sup>2+<\/jats:sup> concentration in human cells. In tumoral pituitaries, BIM-23A760 also inhibited Ca<jats:sup>2+<\/jats:sup> concentration, hormone secretion\/expression and proliferation. However, BIM-23A760 elicited stimulatory effects in a subset of GHomas, ACTHomas and NFPAs in terms of Ca<jats:sup>2+<\/jats:sup> signaling and\/or hormone secretion, which was associated with the relative somatostatin\/dopamine-receptors levels, especially sst5 and sst5TMD4. The chimeric sst2\/sst5\/D<jats:sub>2<\/jats:sub> compound BIM-23A760 affects multiple, clinically relevant parameters on pituitary adenomas and may represent a valuable therapeutic tool. The relative ssts\/D<jats:sub>2<\/jats:sub> expression profile, particularly sst5 and\/or sst5TMD4 levels, might represent useful molecular markers to predict the ultimate response of pituitary adenomas to BIM-23A760.<\/jats:p>","DOI":"10.1038\/srep42002","type":"journal-article","created":{"date-parts":[[2017,2,9]],"date-time":"2017-02-09T10:26:57Z","timestamp":1486636017000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["BIM-23A760 influences key functional endpoints in pituitary adenomas and normal pituitaries: molecular mechanisms underlying the differential response in adenomas"],"prefix":"10.1038","volume":"7","author":[{"given":"Alejandro","family":"Ib\u00e1\u00f1ez-Costa","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura M.","family":"L\u00f3pez-S\u00e1nchez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuel D.","family":"Gahete","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Esther","family":"Rivero-Cort\u00e9s","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mari C.","family":"V\u00e1zquez-Borrego","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda A.","family":"G\u00e1lvez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andr\u00e9s","family":"de la Riva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva","family":"Venegas-Moreno","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis","family":"Jim\u00e9nez-Reina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alberto","family":"Moreno-Carazo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francisco J.","family":"Tinahones","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Maraver-Selfa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miguel A.","family":"Jap\u00f3n","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan A.","family":"Garc\u00eda-Arn\u00e9s","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alfonso","family":"Soto-Moreno","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan M.","family":"Webb","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rhonda D.","family":"Kineman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael D.","family":"Culler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justo P.","family":"Casta\u00f1o","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ra\u00fal M.","family":"Luque","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2017,2,9]]},"reference":[{"key":"BFsrep42002_CR1","doi-asserted-by":"publisher","first-page":"836","DOI":"10.1038\/nrc926","volume":"2","author":"SL Asa","year":"2002","unstructured":"Asa, S. 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