Skip to main content
  • AACR Publications
    • Blood Cancer Discovery
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

AACR logo

  • Register
  • Log in
  • My Cart
Advertisement

Main menu

  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Meeting Abstracts
    • Collections
      • COVID-19 & Cancer Resource Center
      • Focus on Computer Resources
      • Highly Cited Collection
      • Editors' Picks
      • "Best of" Collection
  • For Authors
    • Information for Authors
    • Author Services
    • Early Career Award
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • Editors' Picks
    • OnlineFirst
    • Citations
    • Author/Keyword
    • RSS Feeds
    • My Alert Summary & Preferences
  • News
    • Cancer Discovery News
  • COVID-19
  • Webinars
  • Search More

    Advanced Search

  • AACR Publications
    • Blood Cancer Discovery
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

User menu

  • Register
  • Log in
  • My Cart

Search

  • Advanced search
Cancer Research
Cancer Research
  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Meeting Abstracts
    • Collections
      • COVID-19 & Cancer Resource Center
      • Focus on Computer Resources
      • Highly Cited Collection
      • Editors' Picks
      • "Best of" Collection
  • For Authors
    • Information for Authors
    • Author Services
    • Early Career Award
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • Editors' Picks
    • OnlineFirst
    • Citations
    • Author/Keyword
    • RSS Feeds
    • My Alert Summary & Preferences
  • News
    • Cancer Discovery News
  • COVID-19
  • Webinars
  • Search More

    Advanced Search

Experimental Therapeutics

Protracted Low-Dose Effects on Human Endothelial Cell Proliferation and Survival in Vitro Reveal a Selective Antiangiogenic Window for Various Chemotherapeutic Drugs

Guido Bocci, K. C. Nicolaou and Robert S. Kerbel
Guido Bocci
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
K. C. Nicolaou
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Robert S. Kerbel
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
DOI:  Published December 2002
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

Abstract

Recent preclinical studies have shown that frequent administration in vivo of low doses of chemotherapeutic drugs (“metronomic” dosing) can affect tumor endothelium and inhibit tumor angiogenesis, reducing significant side effects (e.g., myelosuppression) involving other tissues, even after chronic treatment. This suggests that activated endothelial cells may be more sensitive, or even selectively sensitive, to protracted (“high-time”) low-dose chemotherapy compared with other types of normal cells, thus creating a potential therapeutic window. To examine this hypothesis, we assessed the effects of several different chemotherapeutic drugs—namely paclitaxel, 4-hydroperoxycyclophosphamide, BMS-275183 (an oral taxane), doxorubicin, epothilone B (EpoB) and its analogue 5-methylpyridine EpoB—on human microvascular or macrovascular endothelial cells, fibroblasts, and drug-sensitive or multidrug-resistant breast cancer cell lines in cell culture, using both short-term (24 h) versus long-term (144 h), continuous exposures, where drug-containing medium was replaced every 24 h. Whereas little differential and only weak effects were observed using the short-term exposure, a striking trend of comparative vascular endothelial cell hypersensitivity was induced using the continuous long-term exposure protocol. Potent differential growth inhibition effects as well as induction of apoptosis were observed with IC50 values in the range of 25–143 pm for paclitaxel, BMS-275183, EpoB, and 5-methylpyridine-EpoB. In contrast, the IC50 values for tumor cells and fibroblasts tested were in the range of 500 pm to >1 nm for these drugs. Similar differential IC50 values were noted using 4-hydroperoxycyclophosphamide. The results are consistent with the possibility that continuous low-dose therapy with various chemotherapeutic drugs may have a highly selective effect against cycling vascular endothelial cells, and may be relevant to the use of continuous or frequent administration of low doses of certain types of drugs as an optimal way of delivering antiangiogenic therapy.

Footnotes

  • The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

  • ↵1 Supported by a grant from the NIH Service (CA41223; to R. S. K.). G. B. is financially supported by the Italian Society of Pharmacology and by an international scholarship of the Interdepartmental Centre of Clinical Pharmacology and Experimental Therapeutics, University of Pisa, generously donated by the Ente Cassa di Risparmio di Lucca.

  • ↵2 To whom requests for reprints should be addressed, at Sunnybrook and Women’s College Health Sciences Centre, Molecular and Cell Biology Research, S-218, 2075 Bayview Avenue, Toronto, Ontario, M4N 3M5 Canada. Phone: (416) 480-5711; Fax: (416) 480-5703; E-mail: robert.kerbel{at}swchsc.on.ca

  • Received July 12, 2002.
  • Accepted September 27, 2002.
  • ©2002 American Association for Cancer Research.
View Full Text
PreviousNext
Back to top
Cancer Research: 62 (23)
December 2002
Volume 62, Issue 23
  • Table of Contents

Sign up for alerts

View this article with LENS

Open full page PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Cancer Research article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Protracted Low-Dose Effects on Human Endothelial Cell Proliferation and Survival in Vitro Reveal a Selective Antiangiogenic Window for Various Chemotherapeutic Drugs
(Your Name) has forwarded a page to you from Cancer Research
(Your Name) thought you would be interested in this article in Cancer Research.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Protracted Low-Dose Effects on Human Endothelial Cell Proliferation and Survival in Vitro Reveal a Selective Antiangiogenic Window for Various Chemotherapeutic Drugs
Guido Bocci, K. C. Nicolaou and Robert S. Kerbel
Cancer Res December 1 2002 (62) (23) 6938-6943;

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Protracted Low-Dose Effects on Human Endothelial Cell Proliferation and Survival in Vitro Reveal a Selective Antiangiogenic Window for Various Chemotherapeutic Drugs
Guido Bocci, K. C. Nicolaou and Robert S. Kerbel
Cancer Res December 1 2002 (62) (23) 6938-6943;
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • INTRODUCTION
    • MATERIALS AND METHODS
    • RESULTS
    • DISCUSSION
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • PDF
Advertisement

Related Articles

Cited By...

More in this TOC Section

  • Mammary Carcinoma Suppression by Cellular Retinoic Acid Binding Protein-II
  • E1A, E1B Double-restricted Adenovirus for Oncolytic Gene Therapy of Gallbladder Cancer
  • All-trans-Retinoic Acid Eliminates Immature Myeloid Cells from Tumor-bearing Mice and Improves the Effect of Vaccination
Show more Experimental Therapeutics
  • Home
  • Alerts
  • Feedback
  • Privacy Policy
Facebook  Twitter  LinkedIn  YouTube  RSS

Articles

  • Online First
  • Current Issue
  • Past Issues
  • Meeting Abstracts

Info for

  • Authors
  • Subscribers
  • Advertisers
  • Librarians

About Cancer Research

  • About the Journal
  • Editorial Board
  • Permissions
  • Submit a Manuscript
AACR logo

Copyright © 2021 by the American Association for Cancer Research.

Cancer Research Online ISSN: 1538-7445
Cancer Research Print ISSN: 0008-5472
Journal of Cancer Research ISSN: 0099-7013
American Journal of Cancer ISSN: 0099-7374

Advertisement