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肢端肥大症中的生长抑素受体配体:临床反应及预测耐药的因素

Somatostatin receptor ligands in acromegaly: clinical response and factors predicting resistance.

作者信息

Paragliola Rosa Maria, Corsello Salvatore Maria, Salvatori Roberto

机构信息

Unit of Endocrinology, Università Cattolica del Sacro Cuore, Largo Agostino Gemelli 8, 00168, Rome, Italy.

Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Pituitary Center, Johns Hopkins University School of Medicine, 1830 East Monument Street Suite #333, Baltimore, MD, 21287, USA.

出版信息

Pituitary. 2017 Feb;20(1):109-115. doi: 10.1007/s11102-016-0768-4.

Abstract

INTRODUCTION

Somatostatin (SST) receptor ligands (SRL), in particular those of first generation (Octreotide and Lanreotide), are widely used in medical treatment of acromegaly, but they assure biochemical control of disease (and the possibility of an improvement of clinical symptoms and tumor shrinkage), only in a subset of patients.

DISCUSSION

The mechanisms underlying the so called "SRL resistance" are various and involve in particular SST receptor expression and molecular pathways of signal transduction. Different predictors of SRL response have been reported, including clinical and biochemical features (gender, age, growth hormone and insulin-like growth factor-I levels at diagnosis), and tumor characteristic (both at preoperative magnetic resonance imaging study and histopathology) as well as expression of SST receptors. In some cases, only a "partial resistance" to SST can be detected, probably due to the presence of other impaired molecular mechanisms involved in signal transduction, which compromise specific pathways and not others. This may explain some cases of dissociated response between biochemical control and tumor shrinkage.

摘要

引言

生长抑素(SST)受体配体(SRL),尤其是第一代(奥曲肽和兰瑞肽),广泛用于肢端肥大症的医学治疗,但仅在部分患者中能确保疾病的生化控制(以及改善临床症状和肿瘤缩小的可能性)。

讨论

所谓“对SRL耐药”的潜在机制多种多样,尤其涉及SST受体表达和信号转导的分子途径。已报道了不同的SRL反应预测指标,包括临床和生化特征(性别、年龄、诊断时的生长激素和胰岛素样生长因子-I水平)、肿瘤特征(术前磁共振成像研究和组织病理学)以及SST受体的表达。在某些情况下,可能仅检测到对SST的“部分耐药”,这可能是由于存在其他参与信号转导的受损分子机制,这些机制损害了特定途径而非其他途径。这可能解释了生化控制与肿瘤缩小之间出现解离反应的一些病例。

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