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生长抑素类似物对分泌生长激素释放激素的支气管类癌的体外作用

Somatostatin analogs in vitro effects in a growth hormone-releasing hormone-secreting bronchial carcinoid.

作者信息

Zatelli Maria Chiara, Maffei Pietro, Piccin Daniela, Martini Chiara, Rea Federico, Rubello Domenico, Margutti Angelo, Culler Michael D, Sicolo Nicola, degli Uberti Ettore C

机构信息

Section of Endocrinology, Department of Biomedical Sciences and Advanced Therapies, University of Ferrara, Via Savonarola 9, 44100 Ferrara, Italy.

出版信息

J Clin Endocrinol Metab. 2005 Apr;90(4):2104-9. doi: 10.1210/jc.2004-2156. Epub 2005 Jan 25.

Abstract

A 29-yr-old woman presented with acromegaly, pituitary gland enlargement, and an isolated pulmonary mass of 3.3 cm in diameter, which displayed a very high tracer uptake after OctreoScan. Plasma GHRH levels were markedly elevated. The patient underwent left lung upper lobectomy, and histopathology disclosed a bronchial atypical carcinoid. The tissue was examined for somatostatin (SRIH) receptor subtypes (SSTRs) 1-5 expression by RT-PCR. Cultured tumor cells were treated with SRIH, lanreotide (BIM-23014), or SRIH analogs selective for SSTR2 (BIM-23120), SSTR5 (BIM-23206), or SSTR1 (BIM-23926). GHRH was measured in the medium after 6 h, and cell viability was assessed after 48 h. RT-PCR analysis showed expression of SSTR1, -2, and -5. GHRH secretion was significantly reduced by SRIH (-50%), Lan (-35%), as well as by the SSTR2, SSTR5, and SSTR1 selective agonists (-55, -75, and -20%, respectively), whereas cell viability was not affected. Our data show SSTR expression in a GHRH-secreting bronchial carcinoid and provide evidence that, in vitro, selective SSTR activation differently inhibit ectopic GHRH secretion. These findings suggest that SSTR-specific SRIH analogs may be useful in the medical therapy of GHRH-secreting bronchial carcinoids.

摘要

一名29岁女性表现为肢端肥大症、垂体增大,以及一个直径3.3 cm的孤立性肺肿块,奥曲肽扫描后该肿块显示出非常高的示踪剂摄取。血浆生长激素释放激素(GHRH)水平显著升高。患者接受了左肺上叶切除术,组织病理学显示为支气管非典型类癌。通过逆转录聚合酶链反应(RT-PCR)检测该组织中生长抑素(SRIH)受体亚型(SSTRs)1 - 5的表达。用SRIH、兰瑞肽(BIM - 23014)或对SSTR2(BIM - 23120)、SSTR5(BIM - 23206)或SSTR1(BIM - 23926)具有选择性的SRIH类似物处理培养的肿瘤细胞。6小时后测定培养基中的GHRH,48小时后评估细胞活力。RT-PCR分析显示SSTR1、-2和-5有表达。SRIH(-50%)、兰瑞肽(-35%)以及SSTR2、SSTR5和SSTR1选择性激动剂(分别为-55%、-75%和-20%)显著降低了GHRH分泌,而细胞活力未受影响。我们的数据显示了分泌GHRH的支气管类癌中SSTR的表达,并提供了证据表明,在体外,选择性SSTR激活对异位GHRH分泌有不同程度的抑制作用。这些发现提示SSTR特异性SRIH类似物可能对分泌GHRH的支气管类癌的药物治疗有用。

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