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使用生长抑素类似物(奥曲肽)对低度恶性犬脑膜瘤的细胞毒性:一项体外研究。

Cytotoxicity on low-grade canine meningioma with the use of somatostatin analog (octreotide): An in vitro study.

作者信息

Mandara Maria Teresa, Tognoloni Alessia, Giglia Giuseppe, Baroni Massimo, Falzone Cristian, Calò Pietro, Chiaradia Elisabetta

机构信息

Department of Veterinary Medicine, University of Perugia, Perugia (IT).

Clinica Veterinaria Valdinievole, Monsummano Terme (IT).

出版信息

Neurooncol Adv. 2024 Jul 2;6(1):vdae111. doi: 10.1093/noajnl/vdae111. eCollection 2024 Jan-Dec.

DOI:10.1093/noajnl/vdae111
PMID:39055601
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11272066/
Abstract

BACKGROUND

Meningioma is the most common tumor of the central nervous system of dogs. For this tumor, surgery remains the treatment of choice, either alone or in combination with radiotherapy. Unfortunately, chemotherapeutic strategies are practically absent in dogs and palliative therapies are the only option to surgery. Somatostatin receptor subtype 2 (SSTR2) is expressed in canine meningioma. Since the potent cell-proliferation inhibiting effect of somatostatin (SST), the aim of this study was to investigate in vitro the effects of octreotide, as SST analog, in the viability of canine meningioma.

METHODS

Four surgical canine meningiomas were used in this study to establish cell cultures. Expression of SSTR2 was verified with immunolabelling in FFPE samples and cell cultures. The effects of octreotide on cell viability were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT). After 24 hours they were exposed to different concentrations of octreotide (0.1 nM, 1 nM, 10 nM, 100 nM) for 24 and 48 hours.

RESULTS

All meningiomas consisted of grade I tumors. The cultured neoplastic cells expressed SSTR2 from 80% to 100%. Octreotide significantly increased cell death after 48 hours of continuous exposure, with 10 and 100 nM octreotide doses. The percentage of cell viability was 80.92 ± 4.9 and 80.49 ± 3.61, compared to the control, respectively, consistent with decreased cell viability of about 20% for both doses.

CONCLUSIONS

Octreotide reduced the alive neoplastic cultured cells of low-grade canine meningioma in a dose-dependent pattern with continuous exposition for 48 hours. These results support an alternative systemic treatment of meningioma with octreotide in the dog.

摘要

背景

脑膜瘤是犬中枢神经系统最常见的肿瘤。对于这种肿瘤,手术仍然是首选治疗方法,可单独使用或与放疗联合使用。不幸的是,犬类的化疗策略几乎不存在,姑息治疗是手术之外的唯一选择。生长抑素受体2型(SSTR2)在犬脑膜瘤中表达。鉴于生长抑素(SST)具有强大的细胞增殖抑制作用,本研究旨在体外研究奥曲肽(一种SST类似物)对犬脑膜瘤细胞活力的影响。

方法

本研究使用4例手术切除的犬脑膜瘤建立细胞培养物。通过免疫标记在福尔马林固定石蜡包埋(FFPE)样本和细胞培养物中验证SSTR2的表达。通过3-(4,5-二甲基噻唑-2-基)-2,5-二苯基-2H-四唑溴盐(MTT)评估奥曲肽对细胞活力的影响。24小时后,将它们暴露于不同浓度的奥曲肽(0.1 nM、1 nM、10 nM、100 nM)中24小时和48小时。

结果

所有脑膜瘤均为I级肿瘤。培养的肿瘤细胞中80%至100%表达SSTR2。连续暴露48小时后,10 nM和100 nM剂量的奥曲肽显著增加细胞死亡。与对照组相比,细胞活力百分比分别为80.92±4.9和80.49±3.61,两种剂量的细胞活力均下降约20%。

结论

奥曲肽以剂量依赖方式降低了低级别犬脑膜瘤的肿瘤培养活细胞,持续暴露48小时。这些结果支持用奥曲肽对犬脑膜瘤进行替代性全身治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d873/11272066/1f0ec0eefcd2/vdae111_fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d873/11272066/1849b77c02b8/vdae111_fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d873/11272066/1f0ec0eefcd2/vdae111_fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d873/11272066/1849b77c02b8/vdae111_fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d873/11272066/1f0ec0eefcd2/vdae111_fig2.jpg

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本文引用的文献

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Domestic Animal Models of Central Nervous System Tumors: Focus on Meningiomas.中枢神经系统肿瘤的家畜模型:聚焦于脑膜瘤
Life (Basel). 2023 Nov 30;13(12):2284. doi: 10.3390/life13122284.
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Standardization of canine meningioma grading: Validation of new guidelines for reproducible histopathologic criteria.犬脑膜瘤分级的标准化:新的可重现组织病理学标准的验证。
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Meningiomas and Somatostatin Analogs: A Systematic Scoping Review on Current Insights and Future Perspectives.
脑膜瘤与生长抑素类似物:当前认识与未来展望的系统范围综述。
Int J Mol Sci. 2023 Mar 1;24(5):4793. doi: 10.3390/ijms24054793.
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Hormone therapies in meningioma-where are we?脑膜瘤的激素治疗——我们现在处于什么阶段?
J Neurooncol. 2023 Jan;161(2):297-308. doi: 10.1007/s11060-022-04187-1. Epub 2022 Nov 23.
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Somatostatin analogues in treatment-refractory meningioma: a systematic review with meta-analysis of individual patient data.治疗抵抗性脑膜瘤中的生长抑素类似物:一项系统评价和个体患者数据荟萃分析。
Neurosurg Rev. 2022 Oct;45(5):3067-3081. doi: 10.1007/s10143-022-01849-6. Epub 2022 Aug 19.
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Immunoexpression of epithelial membrane antigen in canine meningioma: Novel results for perspective considerations.犬脑膜瘤上皮膜抗原的免疫表达:有前景的考虑的新结果。
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Everolimus and Octreotide for Patients with Recurrent Meningioma: Results from the Phase II CEVOREM Trial.依维莫司与奥曲肽治疗复发性脑膜瘤患者:CEVOREM Ⅱ期试验结果。
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