Mobilization of CTCs after various types of therapy, such as radiation therapy, has been reported, but systematic study of CTCs after chemotherapy remained quite limited. In this study, we sequentially examined CTC numbers after single-dose and repetitive-dose chemotherapy, including FORFIRINOX (FFX) and Gemcitabine and nab-Paclitaxel (GnP) using two pancreatic cancer xenograft models. CTC was detected by the immunocytology-based microfluidic platform. We further examined the dynamic change in the histology of primary tumor tissues during chemotherapy. We confirmed a transient increase in CTCs 1–2 weeks after single-dose and repetitive-dose of FFX/GnP chemotherapy. Histological examination of the primary tumors revealed that the peak period of CTC at 1–2 weeks after chemotherapy corresponded to the maximal destructive phase consisting of cell cycle arrest, apoptosis of tumor cells, and blood vessel destruction without secondary reparative tissue reactions and regeneration of tumor cells. These findings indicate that mobilization of CTCs early after chemotherapy is mediated by the shedding of degenerated tumor cells into the disrupted blood vessels driven by the pure destructive histological changes in primary tumor tissues. These results suggest that sequential CTC monitoring during chemotherapy can be a useful liquid biopsy diagnostic tool to predict tumor chemosensitivity and resistance in preclinical and clinical settings.
已有报道指出，在放疗等多种治疗后会出现循环肿瘤细胞（CTCs）的动员现象，但关于化疗后CTCs的系统性研究仍相当有限。本研究采用两种胰腺癌异种移植模型，对单次及重复剂量化疗（包括FORFIRINOX方案及吉西他滨联合白蛋白结合型紫杉醇方案）后的CTC数量进行了动态监测。通过基于免疫细胞学的微流控平台检测CTC，并进一步观察化疗期间原发肿瘤组织病理学的动态变化。研究证实，在单次及重复剂量FORFIRINOX/吉西他滨联合白蛋白结合型紫杉醇化疗后1-2周，CTC数量出现短暂性升高。原发肿瘤的组织学检查显示，化疗后1-2周CTC的峰值期对应着以细胞周期阻滞、肿瘤细胞凋亡和血管破坏为主要特征的最大组织破坏阶段，此阶段未出现继发性修复组织反应及肿瘤细胞再生。这些发现表明，化疗早期CTC的动员是由原发肿瘤组织发生单纯破坏性病理改变后，退变的肿瘤细胞脱落至受损血管中所介导。研究结果提示，在化疗过程中进行CTC动态监测，可作为一种有效的液体活检诊断工具，用于临床前及临床环境中预测肿瘤化疗敏感性与耐药性。
肿瘤(癌症)患者之家