Combination therapy of transcatheter arterial chemoembolization and arterial administration of antiangiogenesis on VX2 liver tumor

Cardiovasc Intervent Radiol. 2011 Aug;34(4):824-32. doi: 10.1007/s00270-011-0179-x. Epub 2011 Jun 14.

Abstract

Purpose: This study was designed to evaluate the antitumorigenic efficiency of Endostar (an antiangiogenic agent) arterially administrated combined with transcatheter arterial chemoembolization (TACE) on liver tumor, and validation of perfusion CT for quantitative measurements of the results.

Experimental design: Thirty rabbits bearing VX2 liver tumors were randomly and equally distributed into three groups. One of the following treatment protocols was performed in each group: 1) group 1 was treated with TACE and simultaneously arterially administrated Endostar; 2) group 2 with TACE alone, and 3) a control group that had saline injected through hepatic artery. Routine CT scan was performed before treatment, and perfusion CT imaging was performed 2 weeks after treatment. Immunohistochemical biomarkers of microvascular density (MVD) and the expression of vascular endothelial growth factor (VEGF) were measured for assessments of angiogenesis.

Results: We observed a statistically significant reduction from the control in the volume, growth rate, and size of the tumor 2 weeks after treatment with both TACE plus Endostar and with TACE alone (P < 0.01). Although there was no statistically significant difference in tumor size between the group with TACE plus Endostar and the group with TACE alone (P > 0.05), MVD and VEGF were significantly less expressed in the TACE plus Endostar group than both groups with TACE alone and the control group (P < 0.01). Blood flow (BF), blood volume (BV), and permeability-surface area products (PS) in the group with TACE plus Endostar on perfusion CT were significantly higher than other two groups (P < 0.05), which were positively correlated with the MVD and VEGF values (P < 0.05).

Conclusions: TACE with arterial administration of Endostar simultaneously significantly inhibited the angiogenesis biomarkers associated with TACE in a rabbit model bearing VX2 liver tumor, which indicates that the combined treatment protocol may have potential synergistic effects on liver cancer. It also is suggested that perfusion CT may be useful for monitoring antiangiogenic/antivascular treatment in the liver tumors.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / administration & dosage*
  • Angiography
  • Animals
  • Chemoembolization, Therapeutic / methods*
  • Combined Modality Therapy
  • Disease Models, Animal
  • Endostatins / administration & dosage*
  • Image Enhancement
  • Image Processing, Computer-Assisted
  • Infusions, Intra-Arterial / methods*
  • Liver Neoplasms, Experimental / blood supply
  • Liver Neoplasms, Experimental / pathology
  • Liver Neoplasms, Experimental / therapy*
  • Neoplasm Transplantation
  • Rabbits
  • Recombinant Proteins / administration & dosage
  • Tomography, X-Ray Computed
  • Tumor Burden / drug effects
  • Vascular Endothelial Growth Factor A / analysis

Substances

  • Angiogenesis Inhibitors
  • Endostatins
  • Recombinant Proteins
  • Vascular Endothelial Growth Factor A