Antiangiogenesis therapy using a novel angiogenesis inhibitor, anginex, following radiation causes tumor growth delay.

Abstract

BACKGROUND:

The present study investigated whether treatment with anginex, a novel antiangiogenic peptide, could block re-vascularization after radiation treatment.

METHODS:

A squamous cell (SCCVII) xenograft tumor mouse model was employed to assess the effects of anginex given post-radiation on tumor growth, microvessel density (MVD), and oxygen levels. The oxygen status was determined by the partial pressure of O2.

RESULTS:

Tumors in untreated mice increased threefold in 7.0 days, anginex-treated tumors (10 mg/kg intraperitoneal, twice) required 7.3 +/- 0.9 days, and tumors exposed to 8-Gy radiation increased threefold over 11 days. Combination treatment of anginex and radiation caused the tumors to grow threefold in 16.1 +/- 1.6 days, a delay which was significant and deemed supra-additive. Oxygen levels in tumors treated by stand-alone or combination therapies were significantly reduced; for example from 19.5 +/- 4.9 mmHg in controls to 9.7 +/- 1.9 mmHg in combination-treated, size-matched tumors. In addition, immunohistochemistry showed a decrease in MVD in the tumors treated with anginex, radiation, or the combination. These results suggest that a combination of anginex and radiation can greatly affect the amount of functional vasculature in tumors and prolong radiation-induced tumor regression.

CONCLUSION:

Antiangiogenesis therapy with anginex, in addition to radiotherapy, will be useful by blocking angiogenesis-dependent regrowth of vessels.

• Authors: Morikazu Amano, Minoru Suzuki, Satoshi Andoh, Hajime Monzen, Kaoru Terai, Brent Williams, Chang W Song, Kevin H Mayo, Takeo Hasegawa, Ruud P M Dings, Robert J Griffin
• Journal: International journal of clinical oncology (Int J Clin Oncol) Vol. 12 Issue 1 Pg. 42-7 (Feb 2007) ISSN: 1341-9625 [Print] Japan
• PMID: 17380440 (Publication Type: Journal Article)

Chemical References

• Angiogenesis Inhibitors
• Peptides
• Proteins
• betapep-25 protein, synthetic
• Oxygen

Topics

• Angiogenesis Inhibitors (adverse effects, pharmacology)
• Animals
• Blood Vessels (drug effects, radiation effects)
• Carcinoma, Squamous Cell (blood supply, drug therapy, radiotherapy)
• Cell Survival (drug effects, radiation effects)
• Combined Modality Therapy
• Endothelial Cells (drug effects, radiation effects)
• Immunohistochemistry
• Male
• Mice
• Mice, Inbred C3H
• Neoplasms, Experimental
• Neovascularization, Pathologic (drug therapy, pathology, radiotherapy)
• Oxygen (analysis)
• Peptides
• Proteins (pharmacology)
• Skin (blood supply)
• Time Factors
• Tumor Burden
• Tumor Cells, Cultured
• Vascular Neoplasms (blood supply, drug therapy, radiotherapy)
• Xenograft Model Antitumor Assays