The effect of prinomastat (AG3340), a synthetic inhibitor of matrix metalloproteinases, on uveal melanoma rabbit model.
OBJECTIVE
We studied the effects of intravitreally administered prinomastat on the take rate and growth of uveal melanoma after xenograft implantation in rabbit uveal melanoma model.


METHODS
Uveal melanoma xenograft was implanted to suprachoroidal space in each eye of 24 pigmented rabbits which were immunosuppressed with cyclosporine. One week after surgery, the eyes were randomized to receive prinomastat or the vehicle of the prinomastat intravitreally every week for 4 weeks. The take rate of the xenograft, tumor height, apoptosis, and necrosis in the eyes which developed tumors from the treatment and control groups were compared.


RESULTS
A tumor mass was identified in 8 of 24 (33%) prinomastat-treated eyes and 20 of 24 (83%) of the vehicle-treated eyes. Echographic measurements revealed a mean tumor height of 2.2 mm in the prinomastat-treated group and 3.8 mm in the control group in those eyes with take of tumor (p < 0.001). Stereomicroscopic measurements showed a mean tumor height of 1.9 mm in the treatment group and 3.9 mm in the control group (p < 0.001). The mean number of apoptotic nuclei detected per mm(2) of the histologic section in the non-necrotic tumor was 8.12 in the prinomastat-treated group and 0.57 in the control group (p < 0.001). Evaluation of the digital images in microscopic sections of the tumors on histologic slides revealed 29.6% necrosis in prinomastat-treated eyes as compared to 10.9% in vehicle-treated eyes (p = 0.003).


CONCLUSIONS
These results suggest that prinomastat treatment significantly reduces the take rate and the growth rate of xenograft in uveal melanoma rabbit model.
Shiley Eye Center, University of California San Diego, 9415 Campus Point Drive, La Jolla, CA 92093-0946, USA.
Ugur
U
Ozerdem
Beata
B
Mach-Hofacre
Nissi
N
Varki
Robert
R
Folberg
Arthur J
AJ
Mueller
Renata
R
Ochabski
Tony
T
Pham
Krzysztof
K
Appelt
William R
WR
Freeman
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005654:Fundus Oculi; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D008546:Melanoma, Experimental / Q000473:pathology* / Q000503:physiopathology; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D009930:Organic Chemicals; D011817:Rabbits; D014183:Transplantation, Heterologous; D014604:Uveal Neoplasms / Q000473:pathology* / Q000503:physiopathology
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D009930:Organic Chemicals; C113282:prinomastat