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间皮瘤和肺癌中肿瘤球体模型的优化以及H2052/484球体中的抗癌药物测试。

Optimization of tumor spheroid model in mesothelioma and lung cancers and anti-cancer drug testing in H2052/484 spheroids.

作者信息

Gendre Dylan A J, Ameti Edis, Karenovics Wolfram, Perriraz-Mayer Nadja, Triponez Frédéric, Serre-Beinier Véronique

机构信息

Division of Thoracic and Endocrine Surgery, University Hospitals and University of Geneva, 1211 Geneva 4, Switzerland.

出版信息

Oncotarget. 2021 Nov 23;12(24):2375-2387. doi: 10.18632/oncotarget.28134.

Abstract

Advanced lung cancers and mesothelioma remain incurable diseases. Despite some promising new therapy strategies, predicting whether an individual patient will be sensitive to a given therapy is challenging. The purpose of this study is to establish and evaluate the efficiency of a three-dimensional spheroid model of human thoracic cancer in predicting the efficacy of drugs. Human mesothelioma and lung tumor spheroids were established from cell lines and primary cells derived from the patient. The growth kinetics and cell viability of microtumors were assessed using spheroid size and intracellular ATP level. The sensitivity of the mesothelioma spheroids to the cisplatin or cisplatin/pemetrexed combination was determined. We determined that studying the kinetics of the spheroid growth for 15 days after seeding 1000 cells/well in a 96-well plate was optimal. Monitoring the growth kinetic and intracellular ATP of spheroids allowed the identification of early changes in spheroid viability. Finally, we validated this model by measuring a dose-dependent reduction in the cell viability of mesothelioma H2052/484 spheroids treated with both first-line treatments, cisplatin and the cisplatin/pemetrexed combination. In conclusion, we have developed a three-dimensional spheroid model of thoracic tumor cells useful for tailoring the medical treatment to the specific characteristics of each patient.

摘要

晚期肺癌和间皮瘤仍然是无法治愈的疾病。尽管有一些有前景的新治疗策略,但预测个体患者是否会对特定治疗敏感具有挑战性。本研究的目的是建立并评估人胸段癌三维球体模型在预测药物疗效方面的效率。人源间皮瘤和肺肿瘤球体由细胞系以及来自患者的原代细胞建立而成。使用球体大小和细胞内ATP水平评估微肿瘤的生长动力学和细胞活力。测定间皮瘤球体对顺铂或顺铂/培美曲塞联合用药的敏感性。我们确定,在96孔板中每孔接种1000个细胞后研究球体生长动力学15天是最佳的。监测球体的生长动力学和细胞内ATP水平能够识别球体活力的早期变化。最后,我们通过测量一线治疗药物顺铂以及顺铂/培美曲塞联合用药处理的间皮瘤H2052/484球体的细胞活力的剂量依赖性降低,验证了该模型。总之,我们建立了一种胸段肿瘤细胞的三维球体模型,可用于根据每位患者的具体特征定制医疗方案。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0a5/8629400/e3371fc1931c/oncotarget-12-2375-g001.jpg

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