Uveal melanoma model with metastasis in rabbits: effects of different doses of cyclosporine A.
OBJECTIVE
To compare the toxicity and efficacy of different doses of cyclosporine A (CsA) in a rabbit model of uveal melanoma.


METHODS
We used four experimental groups: control, no CsA; group 1, 15 to 10 mg/kg/day; group 2, 15 mg/kg/day; and group 3, 20 mg/kg/day. The MKT-BR cell line was implanted in the choroid. All animals underwent ophthalmoscopic evaluation; the animals were weighed and blood levels of CsA, blood urea nitrogen (BUN), creatinine and alanine aminotransferase (ALT) were measured weekly. Necropsies and histologic study were performed to detect intraocular tumors and metastasis.


RESULTS
A difference in survival rates was found between groups 2 and 3 (p = 0.0042). Differences were observed in the mean BUN and creatinine levels (p < 0.001 and p < 0.003, respectively) between groups but not in the ALT. Intraocular tumors were detected ophthalmoscopically in 50%, 65%, and 70% of the animals in groups 1, 2, and 3 respectively, and histologically in 70%, 90%, and 100% of the same groups. Lung metastases were found in 26.8% of animals with intraocular tumors. Differences were observed in mean CsA blood levels between animals with and without histologically demonstrated uveal tumors (p = 0.001) but not in animals with or without metastasis.


CONCLUSIONS
Different doses of CsA affect survival, tumor development and renal toxicity. Metastatic disease is independent of CsA dose and the subsequent CsA blood levels. A blood level of CsA ranging from 500 to 1000 ng/ml and doses of 10 to 15 mg/kg/day may effectively develop this model of uveal melanoma.
Blanco
G
G
Instituto Universitario de Oftalmobiología Aplicada (IOBA), Universidad de Valladolid, Valladolid, Spain. gonzalo@ioba.med.uva.es
Saornil
A M
AM
Domingo
E
E
Diebold
Y
Y
López
R
R
Rábano
G
G
Tutor
C J
CJ
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001806:Blood Urea Nitrogen; D001835:Body Weight; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D005500:Follow-Up Studies; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D007668:Kidney / Q000187:drug effects; D008175:Lung Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000556:secondary*; D008297:Male; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000401:mortality / Q000556:secondary*; D011817:Rabbits; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D014604:Uveal Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D003404:Creatinine; D000410:Alanine Transaminase