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循环肿瘤细胞的体外培养模型:成功率及其与癌症治疗反应的相关性。

An Ex vivo cultivation model for circulating tumor cells: The success rate and correlations with cancer response to therapy.

作者信息

Chiang I-Hsuan, Kuo Hsuan-Chih, Liao Chun-Ta, Kuo Yung-Chia, Yu Shao-Ming, Wang Hung-Ming, Huang Yi-Hui, Nguyen Thi Kim Anh, Wu Min-Hsien, Hsieh Jason Chia-Hsun

机构信息

Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan.

College of Medicine, Chang Gung University, Taoyuan, Taiwan; Division of Hematology-Oncology, Department of Internal Medicine, New Taipei Municipal TuCheng Hospital, New Taipei City, Taiwan.

出版信息

Biomed J. 2025 Feb;48(1):100819. doi: 10.1016/j.bj.2024.100819. Epub 2024 Nov 30.

Abstract

BACKGROUND

Cancer mortality is closely linked to recurrence and distant metastasis, posing challenges in real-time tracking due to the invasiveness of current methods. Circulating tumor cells (CTCs) show promise as potential tools; however, their scarcity remains a significant obstacle.

METHOD

In this prospective study, we validated a simple culture protocol and investigated the correlation between clinical response and CTC growth status. Following negative selection, the isolated cells were subjected to ex vivo cultivation in a two-dimensional environment supplemented with cytokines for up to 21 days, followed by immunofluorescence staining for analysis.

RESULTS

Among 37 participants with solid tumors and distant metastasis (34.8% head and neck cancer), 47 samples were collected, from which CTCs were detected. The percentages of CTCs, atypical CTCs, and white blood cells during cultivation from days 7-21 were significantly different (p < 0.001, p < 0.001, and p = 0.330, respectively). Patients were further categorized into progressive disease (PD) and non-PD groups based on disease status, revealing significant differences in CTC growth rates, which increases from Days 7-21 between groups (5.5x vs. 2.8x growth, respectively; p < 0.001).

CONCLUSION

With the proposed protocols, we cultured CTCs from patients with various cancers for 21 days and identified a tool for predicting cancer response. The actual cancer status (PD or non-PD) at CTC isolation correlates to CTC growth rate, guiding the required observation time and parameters for culture.

摘要

背景

癌症死亡率与复发和远处转移密切相关,由于当前方法具有侵入性,在实时跟踪方面面临挑战。循环肿瘤细胞(CTC)有望成为潜在工具;然而,其稀缺性仍然是一个重大障碍。

方法

在这项前瞻性研究中,我们验证了一种简单的培养方案,并研究了临床反应与CTC生长状态之间的相关性。经过阴性选择后,将分离出的细胞在补充细胞因子的二维环境中进行体外培养长达21天,然后进行免疫荧光染色分析。

结果

在37名患有实体瘤和远处转移的参与者中(34.8%为头颈癌),共采集了47份样本,从中检测到了CTC。培养第7至21天期间,CTC、非典型CTC和白细胞的百分比存在显著差异(分别为p < 0.001、p < 0.001和p = 0.330)。根据疾病状态将患者进一步分为疾病进展(PD)组和非PD组,结果显示两组之间CTC生长率存在显著差异,从第7天到第21天,两组的CTC生长率分别增加(分别为5.5倍和2.8倍;p < 0.001)。

结论

通过所提出的方案,我们将来自各种癌症患者的CTC培养了21天,并确定了一种预测癌症反应的工具。分离CTC时的实际癌症状态(PD或非PD)与CTC生长率相关,可指导所需的观察时间和培养参数。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bcf0/11743102/bd6fb97e80bb/gr1.jpg

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