Morphologic Manifestations of Vascular-disrupting Agents in Preclinical Models

Research output: Chapter in Book/Report/Conference proceedingChapter

7 Scopus citations

Abstract

An important aspect of tumor growth is the continued 'physiologic' functioning of intratumoral blood vessels, effectively delivering oxygen and nutrients. Vascular disrupting agents (VDA) target this component of tumor vasculature, bringing about a rapid and catastrophic shutdown and consequent tumor necrosis. Using three animal tumor models and different VDAs we detail the morphologic and morphometric evolution of VDA induced tumor injury. While there are quantitative and chronologic differences, qualitative morphologic alterations are strikingly similar between the tumor models and VDAs investigated. Functional vascular shutdown is identified by fluorescent microscopy within the first hour following parenteral delivery of the drug. As the tumor undergoes frank necrosis, intratumoral vessels are irreversibly damaged. The pattern of injury is typical of vascular compromise, with necrosis interspersed with areas of red cell extravasation. In each of the models, surviving tumor persists as a peripheral, viable rim of neoplastic elements that has a clear and significant potential for regrowth. The morphologic changes manifest by use of these agents, provide important clues to understanding the mechanisms that operate in the induction of this antitumor activity.

Original languageEnglish (US)
Title of host publicationVascular-Targeted Therapies in Oncology
PublisherJohn Wiley & Sons, Ltd
Pages81-94
Number of pages14
ISBN (Print)9780470012949
DOIs
StatePublished - May 31 2006
Externally publishedYes

Keywords

  • Combretastatin and ZD6126
  • Effects of treatment
  • Human Kaposi's sarcoma (KSY-1) and renal cell carcinoma Caki-1 xenograft
  • Intratumoral vascular damage
  • Targeting tumor vasculature
  • Tumor supportive blood vessel attack
  • Vascular disrupting agents (VDA)
  • Vascular-disrupting agents in preclinical models

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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