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

416 Citations (Scopus)

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

Fingerprint

Metronomic Administration
Drug Therapy
Growth
Neoplasms
Pharmaceutical Preparations
Cyclophosphamide
Blood Vessels
Lymphoma
Appointments and Schedules
Stem Cells
Endothelial Progenitor Cells

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Maximum tolerable dose and low-dose metronomic chemotherapy have opposite effects on the mobilization and viability of circulating endothelial progenitor cells. / Bertolini, Francesco; Paul, Saki; Mancuso, Patrizia; Monestiroli, Silvia; Gobbi, Alberto; Shaked, Yuval; Kerbel, Robert S.

In: Cancer Research, Vol. 63, No. 15, 01.08.2003, p. 4342-4346.

Research output: Contribution to journalArticle

@article{83d384bdca2a4c6ba44fb3da0fb998cd,
title = "Maximum tolerable dose and low-dose metronomic chemotherapy have opposite effects on the mobilization and viability of circulating endothelial progenitor cells",
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.",
author = "Francesco Bertolini and Saki Paul and Patrizia Mancuso and Silvia Monestiroli and Alberto Gobbi and Yuval Shaked and Kerbel, {Robert S.}",
year = "2003",
month = "8",
day = "1",
language = "English",
volume = "63",
pages = "4342--4346",
journal = "Journal of Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "15",

}

TY - JOUR

T1 - Maximum tolerable dose and low-dose metronomic chemotherapy have opposite effects on the mobilization and viability of circulating endothelial progenitor cells

AU - Bertolini, Francesco

AU - Paul, Saki

AU - Mancuso, Patrizia

AU - Monestiroli, Silvia

AU - Gobbi, Alberto

AU - Shaked, Yuval

AU - Kerbel, Robert S.

PY - 2003/8/1

Y1 - 2003/8/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0041589524&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0041589524&partnerID=8YFLogxK

M3 - Article

VL - 63

SP - 4342

EP - 4346

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0008-5472

IS - 15

ER -