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基于球体的3D细胞培养可实现头颈癌的个性化治疗测试和药物发现。

Spheroid-based 3D Cell Cultures Enable Personalized Therapy Testing and Drug Discovery in Head and Neck Cancer.

作者信息

Hagemann Jan, Jacobi Christian, Hahn Moritz, Schmid Vanessa, Welz Christian, Schwenk-Zieger Sabina, Stauber Roland, Baumeister Philipp, Becker Sven

机构信息

Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Center of Johannes-Gutenberg University, Mainz, Germany.

Department of Otorhinolaryngology, Head and Neck Surgery, Ludwig-Maximilian-University Medical Center, Munich, Germany.

出版信息

Anticancer Res. 2017 May;37(5):2201-2210. doi: 10.21873/anticanres.11555.

Abstract

BACKGROUND/AIM: Chemo-radiation currently serves as first-line therapy of advanced and recurrent head and neck cancer, while new chemotherapy regimens are emerging. However, response rates to any treatment are difficult to predict and underlie broad variation. This study shows the development of a standardized, high-throughput in vitro assay to assess patients' individual response to therapy regimens as a future tool for personalized tumor therapy.

MATERIALS AND METHODS

Viability and proliferation analyses after chemo +/- radiation treatment of single spheroids (low adhesion plates/Hanging Drop (HD)) were generated from head and neck squamous cell carcinoma (HNSCC) cell lines and primary human cells from fresh tumor specimens.

RESULTS

All cell lines showed reliable growth in all cell culture methods. The spheroids showed significant delay of growth and/or necrosis compared to control groups when exposed to current standard chemotherapeutic regimens. Single 3D spheroids ready for therapy susceptibility testing could be generated from actual tumor specimens after enzymatic and mechanical separation.

CONCLUSION

In its current form, this single spheroid-based in vitro assay was able to test individual therapy susceptibility to current standard therapy regimens or, potentially, for testing new targeted drugs in HNSCC treatment. With recent discoveries regarding tumor heterogeneity and individual mutation status, a reliable assay is a prerequisite for personalized therapy in head and neck cancer.

摘要

背景/目的:化疗联合放疗目前是晚期和复发性头颈癌的一线治疗方法,同时新的化疗方案不断涌现。然而,任何治疗的反应率都难以预测,且存在很大差异。本研究展示了一种标准化、高通量的体外检测方法的开发,以评估患者对治疗方案的个体反应,作为未来个性化肿瘤治疗的工具。

材料与方法

从头颈鳞状细胞癌(HNSCC)细胞系和新鲜肿瘤标本中的原代人细胞生成单球体(低粘附板/悬滴法(HD))经化疗±放疗后的活力和增殖分析。

结果

所有细胞系在所有细胞培养方法中均显示出可靠的生长。与对照组相比,当暴露于当前标准化疗方案时,球体显示出生长显著延迟和/或坏死。在酶解和机械分离后,可从实际肿瘤标本中生成用于治疗敏感性测试的单个3D球体。

结论

以目前的形式,这种基于单球体的体外检测方法能够测试个体对当前标准治疗方案的治疗敏感性,或者潜在地用于测试头颈鳞状细胞癌治疗中的新靶向药物。随着最近关于肿瘤异质性和个体突变状态的发现,可靠的检测方法是头颈癌个性化治疗的先决条件。

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