关键词: carcinoma neuroendocrine tumors pasireotide somatostatin receptors

Mesh : Humans Octreotide / therapeutic use pharmacology Somatostatin / analogs & derivatives therapeutic use pharmacology Neuroendocrine Tumors / drug therapy Receptors, Somatostatin / analysis Retrospective Studies Male Middle Aged Female Aged Cell Line, Tumor Cell Proliferation / drug effects Adult Antineoplastic Agents, Hormonal / therapeutic use pharmacology Antineoplastic Agents / therapeutic use pharmacology

来  源:   DOI:10.3390/medicina60071039   PDF(Pubmed)

Abstract:
Background and Objectives: High-grade malignant neuroendocrine tumors (G3 NETs) and neuroendocrine carcinomas (NECs) are characterized by rapid proliferation, high metastatic capacity, and strong expression of somatostatin receptors (SSTRs). We aimed to analyze the presence of SSTRs in NET G3 and NEC, and to correlate their expression with the use of octreotide and pasireotide. Materials and Methods: For this purpose, we first performed a retrospective study of G3 NET and NEC patients, which included the determination of SSTR expression and response to octreotide treatment. Second, we selected the H69 small cell lung cancer cell line to determine the effect of octreotide and pasireotide. Results: Our results showed the traditional somatostatin analog (SSA) octreotide was ineffective in patients with NET G3 and NEC. On the other hand, RT-qPCR showed a high expression of SSTR2 and SSTR5 in H69 cells. Interestingly, while octreotide did not modify H69 cell proliferation, a strong inhibition of proliferation was detected with the use of pasireotide. Conclusions: In view of these results, a clinical trial in NET G3 and NEC patients using pasireotide is necessary to determine the usefulness of this drug in improving patient treatment.
摘要:
背景与目的:高级别恶性神经内分泌肿瘤(G3NETs)和神经内分泌癌(NECs)具有快速增殖的特点,高转移能力,和生长抑素受体(SSTRs)的强表达。我们的目的是分析NETG3和NEC中SSTR的存在,并将它们的表达与奥曲肽和帕瑞肽的使用相关联。材料和方法:为此,我们首先对G3NET和NEC患者进行了回顾性研究,其中包括SSTR表达的测定和对奥曲肽治疗的反应。第二,我们选择了H69小细胞肺癌细胞系来确定奥曲肽和帕瑞肽的作用。结果:我们的结果表明,传统的生长抑素类似物(SSA)奥曲肽在NETG3和NEC患者中无效。另一方面,RT-qPCR显示H69细胞中SSTR2和SSTR5的高表达。有趣的是,而奥曲肽不改变H69细胞增殖,使用pasireotide检测到对增殖的强烈抑制作用。结论:鉴于这些结果,NETG3和NEC患者使用帕瑞肽的临床试验对于确定该药物在改善患者治疗方面的有效性是必要的.
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