Department of Surgery, Oncology and Gastroenterology, Oncology Section, University of Padova, Italy.
Br J Cancer. 2012 Oct 9;107(8):1286-94. doi: 10.1038/bjc.2012.388. Epub 2012 Sep 6.
Recently, we developed an apoptotic assay for expanding the monitoring capabilities of the circulating tumour cells (CTC) test during therapy. An automated platform for computing CTCs was integrated with a mAb (M30) targeting a neoepitope disclosed by caspase cleavage at cytokeratin 18 in early apoptosis; we showed that live CTCs were associated with progression, consistent with enhanced cell migration and invasion. The test was first applied here to mRCC.
Live/apoptotic CTCs changes were measured in mRCC patients receiving first-line Sunitinib and compared with circulating endothelial cell (CEC) levels.
The presence of EpCAM-positive, live CTCs predicts progression in individual mRCC patient, being associated with distant metastasis under first-line Sunitinib. Synchronous detection of CTCs and CEC levels discloses for the first time an association between their dynamic changes and outcome: a rapid increase of the CEC number as early as the first cycle of therapy is associated with CTC decrease in non-progressed patients, whereas a delayed response of CECs is related to higher CTC values in the progressed group indicating treatment failure.
We demonstrated that a delayed response to antiangiogenic treatment indicated by persistent detection of CECs correlates with persistent live CTCs and more aggressive disease.
最近，我们开发了一种凋亡检测方法，以扩展循环肿瘤细胞（CTC）检测在治疗过程中的监测能力。我们将一种针对细胞角蛋白 18 切割后新表位的单抗（M30）与一种自动计算 CTC 的平台集成在一起；我们发现活的 CTC 与进展相关，这与增强的细胞迁移和侵袭一致。该检测方法首次应用于 mRCC。
在接受一线舒尼替尼治疗的 mRCC 患者中测量活/凋亡 CTC 变化，并与循环内皮细胞（CEC）水平进行比较。
EpCAM 阳性、活的 CTCs 的存在预测了个体 mRCC 患者的进展，与一线舒尼替尼下的远处转移有关。首次同步检测 CTC 和 CEC 水平揭示了它们的动态变化与结果之间的关联：治疗的第一个周期中 CEC 数量的快速增加与非进展患者的 CTC 减少相关，而 CEC 的延迟反应与进展组中更高的 CTC 值相关，表明治疗失败。
我们证明，抗血管生成治疗的延迟反应，表现为持续检测到 CECs，与持续存在的活 CTCs 和更具侵袭性的疾病相关。
