Maximum tolerable dose and low-dose metronomic chemotherapy have opposite effects on the mobilization and viability of circulating endothelial progenitor cells

Francesco Bertolini, Saki Paul, Patrizia Mancuso, Silvia Monestiroli, Alberto Gobbi, Yuval Shaked, Robert S. Kerbel

Research output: Contribution to journalArticle

Abstract

There is growing evidence that vasculogenesis (progenitor cell-derived generation of new blood vessels) is required for the growth of some neoplastic diseases. Here we show that the administration of cyclophosphamide (CTX) at the maximum tolerable dose with 21-day breaks or at more frequent low-dose (metronomic) schedules have opposite effects on the mobilization and viability of circulating endothelial progenitors (CEPs) in immunodeficient mice bearing human lymphoma cells. Animals treated with the maximum tolerable dose CTX experienced a robust CEP mobilization a few days after the end of a cycle of drug administration, and tumors rapidly became drug resistant. Conversely, the administration of metronomic CTX was associated with a consistent decrease in CEP numbers and viability and with more durable inhibition of tumor growth. Our findings suggest that metronomic low-dose chemotherapy regimens are particularly promising for avoiding CEP mobilization and, hence, to potentially reduce vasculogenesis-dependent mechanisms of tumor growth.

Original languageEnglish
Pages (from-to)4342-4346
Number of pages5
JournalCancer Research
Volume63
Issue number15
Publication statusPublished - Aug 1 2003

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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