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钙三醇介导的高钙血症、生长抑素受体表达与 GIST 肿瘤中 25-羟维生素 D-1α-羟化酶。

Calcitriol-Mediated Hypercalcemia, Somatostatin Receptors Expression and 25-Hydroxyvitamin D-1α- Hydroxylase in GIST Tumors.

机构信息

Maimonides Institute for Biomedical Research of Córdoba, Cordoba, Spain.

Nuclear Medicine Service, Virgen del Rocio University Hospital, Seville, Spain.

出版信息

Front Endocrinol (Lausanne). 2022 Jan 26;12:812385. doi: 10.3389/fendo.2021.812385. eCollection 2021.

Abstract

Hypercalcemia is a common complication in cancer patients Mainly caused by Parathyroid hormone-related protein (PTHrP) secretion and metastasis. Calcitriol secretion is a rare source of hypercalcemia in solid tumors, especially in gastrointestinal stromal tumors (GIST). We present a case report of a female patient with a 23 cm gastric GIST that expressed somatostatin-receptors and presented with severe hypercalcemia due to calcitriol secretion. Calcium control was achieved with medical treatment before the use of targeted-directed therapies. Surgery was performed and allowed complete tumor resection. Two years later, patient remains free of disease. Molecular analysis revealed the mRNA expression of 25-hydroxyvitamin D-1-hydroxylase (1αOHase) and vitamin-D receptors in the tumor cells, confirming the calcitriol-mediated mechanism. Furthermore, the expression of the endotoxin recognition factors CD14 and TLR4 suggests an inflammatory mediated mechanism. Finally, the expression of somatostatin-receptors, especially might have been related with clinical evolution and prognosis in this patient.

摘要

高钙血症是癌症患者的常见并发症,主要由甲状旁腺激素相关蛋白(PTHrP)分泌和转移引起。1,25-二羟维生素 D3(calcitriol)分泌是实体瘤,特别是胃肠道间质瘤(GIST)中高钙血症的罕见来源。我们报告了一例女性患者,其胃 GIST 长 23 厘米,表达生长抑素受体,并因 1,25-二羟维生素 D3 分泌而出现严重高钙血症。在使用靶向治疗之前,通过药物治疗控制了钙水平。手术完成并允许完全切除肿瘤。两年后,患者无病生存。分子分析显示肿瘤细胞中 25-羟维生素 D-1-羟化酶(1αOHase)和维生素 D 受体的 mRNA 表达,证实了 1,25-二羟维生素 D3 介导的机制。此外,内毒素识别因子 CD14 和 TLR4 的表达表明存在炎症介导的机制。最后,生长抑素受体的表达,特别是 SSTR2,可能与该患者的临床演变和预后有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a97/8826724/92e8d749dfb1/fendo-12-812385-g001.jpg

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