Detection of endothelial progenitor cells in peripheral blood can determine the optimum biologic dose and antitumor effects of metronomic chemotherapy regimens
10.3781/j.issn.1000-7431.2008.07.006
- Author:
Xin WU
1
Author Information
1. Department of Oncology
- Publication Type:Journal Article
- Keywords:
Angiogenesis inhibitors;
Dose-response relationship, drug;
Mice, nude;
Neoplasms;
Peripheral blood stem cell
- From:
Tumor
2008;28(7):567-571
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To assess endothelial progenitor cells (EPCs) in the peripheral blood of SGC-7901, MKN-45, Huh-7 and U87 xenograft in BALB/c nude mice, and to show whether circulating EPCs (CEPs) can serve as a pharmacodynamic biomarkers to determine the optimum biologic dose (OBD) of metronomic UFT. Methods: The tumor-bearing animal models were established. After mice were treated with UFT and CTX, circulating EPC (CEPs) was measured by flow cytometry and microvessel density (MVD) was evaluated in parallel by immunohistochemistry. Results: We found increases in the levels of CEPs in nude mice with SGC-7901, MKN-45, Huh-7, and U87 xenograft compared with control group (P < 0.05). The nude mice with MNK-45 xenograft were treated with various low-dose of UFT continuously. The OBD of UFT chemotherapy against angiogenesis was determined as 20 mg · kg-1 · d-1 as measured by CEP detection. The nude mice were nearly dead after treatment with UFT at maximum tolerable dose for 1 week. The CEP increased significantly compared with control group (P < 0.05). Assessment of CEPs can determine the OBD of metronomic UFT. Maximum tolerable dose and low-dose metronomic chemotherapy of UFT have opposite effects on the mobilization of CEPs. The nude mice xenografted with MNK-45 were treated with UFT and CTX at low dose continuously. We found that there was correlation between changes in CEPs and inhibition of tumor angiogenesis as measured by microvessel density (r = 0.998, P = 0.044). Conclusion: Detection of CEPs can determine the OBD and antitumor effects of metronomic chemotherapy of UFT.
