Combined immunologic and anti-angiogenic therapy reduces hepatic micrometastases in a murine ocular melanoma model.
OBJECTIVE
To evaluate the combined effect of neoadjuvant intracameral interferon alpha -2b and adjuvant low-dose angiostatin in reducing the number of hepatic micrometastases in a murine model of ocular melanoma.


METHODS
The posterior compartments of the right eyes of C57BL6 mice were inoculated with 5 x 10(5) cells/2.5 microl of cells from the Queens, B16F10, or B16LS9 melanoma cell lines. The right eyes were enucleated at 7 days, and the mice were sacrificed at 28 days postinoculation, respectively. Hepatic micrometastases were counted. There were four treatment groups (n = 15 each) for each cell line as follows: group 1, intraperitoneal injections of 20 KIU interferon alpha -2b for 4 days prior to enucleation; group 2, intramuscular injections of 100 microl 0.1 microg/microl murine angiostatin every day for 14 days starting on day 1 after enucleation; group 3, treatment of group 1 and group 2 combined; group 4, intraperitoneal and intramuscular injections of equal volumes of phosphate-buffered saline (PBS) (control group).


RESULTS
Results showed decreased micrometastases for groups 1 through 3 compared with group 4, with the greatest reduction in group 3 (p < 0.006).


CONCLUSIONS
This study suggests that combined neoadjuvant interferon alpha -2b and adjuvant low-dose angiostatin therapy act synergistically to decrease hepatic micrometastases in a murine ocular melanoma model.
Yang
Hua
H
Department of Ophthalmology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Grossniklaus
Hans E
HE
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D043168:Angiostatins / Q000627:therapeutic use*; D000818:Animals; D004195:Disease Models, Animal; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008545:Melanoma / Q000188:drug therapy* / Q000556:secondary; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured; D014604:Uveal Neoplasms / Q000188:drug therapy* / Q000473:pathology
D020533:Angiogenesis Inhibitors; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D043168:Angiostatins