Abstract
BackgroundThe abundance of circulating endothelial cells (CECs) and circulating endothelial progenitor cells (CEPs), which serve as surrogate markers for angiogenesis, may be affected by chemotherapy. We studied their dynamic change during consecutive cycles of chemotherapy.MethodsWe collected blood samples from 15 breast cancer patients, who received a total of 56 courses of systemic chemotherapy, and measured the CECs, viable CECs (V-CECs), and CEPs by six-color flow cytometry within the seven days prior to chemotherapy, twice a week during the first and second cycles of chemotherapy, and then once a week during the subsequent cycles.ResultsThe CEC, V-CEC, and CEP levels all significantly decreased from day 1 of treatment to the first week of chemotherapy. After one week of chemotherapy, the CEC and V-CEC levels returned to a level similar to day 1. The CEP level remained significantly reduced after the first week of chemotherapy, but gradually rebounded until the next course of chemotherapy. After six cycles of chemotherapy, the total number of CEC and V-CEC cells trended toward a decrease and the CEP cells toward an increase. Clinical factors, including the existence of a tumor, chemotherapy regimens, and the use of granulocyte colony stimulating factor, did not significantly affect these results.ConclusionsThe CEC and CEP counts change dynamically during each course of chemotherapy and after the chemotherapy cycles, providing background data for any future study planning to use CECs and CEPs as surrogate markers of angiogenesis in antiangiogenesis treatments combined with chemotherapy.
Highlights
The abundance of circulating endothelial cells (CECs) and circulating endothelial progenitor cells (CEPs), which serve as surrogate markers for angiogenesis, may be affected by chemotherapy
The timing of the measurement of the CECs and CEPS is important when using them as surrogate markers, especially when antiangiogenesis therapy is combined with maximal tolerated dose (MTD) chemotherapy
CEC and CEP test were preformed within 24 hours of collection of blood samples
Summary
The abundance of circulating endothelial cells (CECs) and circulating endothelial progenitor cells (CEPs), which serve as surrogate markers for angiogenesis, may be affected by chemotherapy. We studied their dynamic change during consecutive cycles of chemotherapy. Chemotherapy with the addition of bevacizumab, an antivascular endothelial growth factor (VEGF) antibody, antiangiogenesis treatments are widely used, we still lack a surrogate marker to select the populations for whom the drug will be effective and to define the optimal biological dose and treatment timing for antiangiogenic therapy. The timing of the measurement of the CECs and CEPS is important when using them as surrogate markers, especially when antiangiogenesis therapy is combined with MTD chemotherapy. To clarify the dynamic pattern of CECs and CEPs, we designed a study to describe the detailed dynamic change of CECs and CEPs during each cycle of chemotherapy treatment
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