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


CONCLUSIONS
Antiangiogenesis therapy with anginex, in addition to radiotherapy, will be useful by blocking angiogenesis-dependent regrowth of vessels.
Amano
Morikazu
M
Department of Radiology, Kakegawa City General Hospital, 1-1-1 Minami Sugiya, Kakegawa, Shizuoka 436-8502, Japan. Morikazu@mail.wbs.ne.jp
Suzuki
Minoru
M
Andoh
Satoshi
S
Monzen
Hajime
H
Terai
Kaoru
K
Williams
Brent
B
Song
Chang W
CW
Mayo
Kevin H
KH
Hasegawa
Takeo
T
Dings
Ruud P M
RP
Griffin
Robert J
RJ
D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D001808:Blood Vessels / Q000187:drug effects / Q000528:radiation effects; D002294:Carcinoma, Squamous Cell / Q000098:blood supply* / Q000188:drug therapy* / Q000532:radiotherapy; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D003131:Combined Modality Therapy; D042783:Endothelial Cells / Q000187:drug effects / Q000528:radiation effects; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009374:Neoplasms, Experimental; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy; D010100:Oxygen / Q000032:analysis; D010455:Peptides; D011506:Proteins / Q000494:pharmacology*; D012867:Skin / Q000098:blood supply; D013997:Time Factors; D047368:Tumor Burden; D014407:Tumor Cells, Cultured; D019043:Vascular Neoplasms / Q000098:blood supply* / Q000188:drug therapy* / Q000532:radiotherapy; D023041:Xenograft Model Antitumor Assays
D020533:Angiogenesis Inhibitors; D010455:Peptides; D011506:Proteins; C111993:betapep-25 protein, synthetic; D010100:Oxygen