Orthotopic glioblastoma stem-like cell xenograft model in mice to evaluate intra-arterial delivery of bevacizumab: from bedside to bench. Academic Article uri icon

Overview

MeSH

  • Animals
  • Bevacizumab
  • Blood-Brain Barrier
  • Blotting, Western
  • Cells, Cultured
  • Electrophoresis, Polyacrylamide Gel
  • Immunohistochemistry
  • Injections, Intra-Arterial
  • Luminescence
  • Male
  • Mice
  • Mice, Nude
  • Neoplastic Stem Cells
  • Stereotaxic Techniques
  • Xenograft Model Antitumor Assays

MeSH Major

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Brain Neoplasms
  • Glioblastoma
  • Neoplasm Transplantation

abstract

  • Bevacizumab (BV), a humanized monocolonal antibody directed against vascular endothelial growth factor (VEGF), is a standard intravenous (IV) treatment for recurrent glioblastoma multiforme (GBM), that has been introduced recently as an intra-arterial (IA) treatment modality in humans. Since preclinical models have not been reported, we sought to develop a tumor stem cell (TSC) xenograft model to investigate IA BV delivery in vivo. Firefly luciferase transduced patient TSC were injected into the cortex of 35 nude mice. Tumor growth was monitored weekly using bioluminescence imaging. Mice were treated with either intraperitoneal (IP) or IA BV, with or without blood-brain barrier disruption (BBBD), or with IP saline injection (controls). Tumor tissue was analyzed using immunohistochemistry and western blot techniques. Tumor formation occurred in 31 of 35 (89%) mice with a significant signal increase over time (p=0.018). Post mortem histology revealed an infiltrative growth of TSC xenografts in a similar pattern compared to the primary human GBM. Tumor tissue analyzed at 24 hours after treatment revealed that IA BV treatment with BBBD led to a significantly higher intratumoral BV concentration compared to IA BV alone, IP BV or controls (p<0.05). Thus, we have developed a TSC-based xenograft mouse model that allows us to study IA chemotherapy. However, further studies are needed to analyze the treatment effects after IA BV to assess tumor progression and overall animal survival. Copyright © 2012 Elsevier Ltd. All rights reserved.

publication date

  • November 2012

has subject area

  • Animals
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Bevacizumab
  • Blood-Brain Barrier
  • Blotting, Western
  • Brain Neoplasms
  • Cells, Cultured
  • Electrophoresis, Polyacrylamide Gel
  • Glioblastoma
  • Immunohistochemistry
  • Injections, Intra-Arterial
  • Luminescence
  • Male
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Neoplastic Stem Cells
  • Stereotaxic Techniques
  • Xenograft Model Antitumor Assays

Research

keywords

  • Journal Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1016/j.jocn.2012.03.012

PubMed ID

  • 22985932

Additional Document Info

start page

  • 1568

end page

  • 1572

volume

  • 19

number

  • 11