Department of Medical Oncology, University Medical Center Utrecht, Utrecht, The Netherlands.
Neoplasia. 2010 Jan;12(1):87-94. doi: 10.1593/neo.91460.
We and others have previously demonstrated that the acute release of progenitor cells in response to chemotherapy actually reduces the efficacy of the chemotherapy. Here, we take these data further and investigate the clinical relevance of circulating endothelial (progenitor) cells (CE(P)Cs) and modulatory cytokines in patients after chemotherapy with relation to progression-free and overall survival (PFS/OS). Patients treated with various chemotherapeutics were included. Blood sampling was performed at baseline, 4 hours, and 7 and 21 days after chemotherapy. The mononuclear cell fraction was analyzed for CE(P)C by FACS analysis. Plasma was analyzed for cytokines by ELISA or Luminex technique. CE(P)Cs were correlated with response and PFS/OS using Cox proportional hazard regression analysis. We measured CE(P)Cs and cytokines in 71 patients. Only patients treated with paclitaxel showed an immediate increase in endothelial progenitor cell 4 hours after start of treatment. These immediate changes did not correlate with response or survival. After 7 and 21 days of chemotherapy, a large and consistent increase in CE(P)C was found (P < .01), independent of the type of chemotherapy. Changes in CE(P)C levels at day 7 correlated with an increase in tumor volume after three cycles of chemotherapy and predicted PFS/OS, regardless of the tumor type or chemotherapy. These findings indicate that the late release of CE(P)C is a common phenomenon after chemotherapeutic treatment. The correlation with a clinical response and survival provides further support for the biologic relevance of these cells in patients' prognosis and stresses their possible use as a therapeutic target.
我们和其他人之前已经证明，化疗后祖细胞的急性释放实际上会降低化疗的疗效。在这里，我们进一步研究了循环内皮（祖）细胞（CE（P）Cs）和调节细胞因子在化疗后患者中的临床相关性，与无进展生存期和总生存期（PFS/OS）有关。包括接受各种化疗药物治疗的患者。在化疗前、化疗后 4 小时、7 天和 21 天进行采血。通过 FACS 分析分析单核细胞部分的 CE（P）C。通过 ELISA 或 Luminex 技术分析血浆中的细胞因子。使用 Cox 比例风险回归分析将 CE（P）C 与反应和 PFS/OS 相关联。我们测量了 71 名患者的 CE（P）C 和细胞因子。只有接受紫杉醇治疗的患者在治疗开始后 4 小时内皮祖细胞立即增加。这些即时变化与反应或生存无关。化疗后 7 天和 21 天，发现 CE（P）C 大量且一致增加（P <.01），与化疗类型无关。第 7 天 CE（P）C 水平的变化与三个化疗周期后肿瘤体积的增加相关，并预测 PFS/OS，无论肿瘤类型或化疗药物如何。这些发现表明，CE（P）C 的晚期释放是化疗后常见的现象。与临床反应和生存的相关性为这些细胞在患者预后中的生物学相关性提供了进一步的支持，并强调了它们作为治疗靶点的潜在用途。
