ABSTRACT
We investigated the need for continuous immunosuppression to maintain experimental tumours derived from human uveal melanoma cells implanted in the choroid of pigmented rabbits. Two groups of pigmented rabbits immunosuppressed with cyclosporin A (CsA) were implanted with human uveal melanoma cells in the suprachoroidal space. After 5 weeks, CsA was discontinued in group 2. Animals were treated with prophylactic antibiotics and examined weekly for tumour growth, weight and secondary effects; blood urea nitrogen levels were measured every two weeks. Autopsies and histopathological studies were performed after death or euthanasia at the end of week 12. The difference between the groups in the development of ophthalmoscopic tumours was not statistically significant 5 weeks after implantation. Tumours in group 1 grew progressively throughout the experiment, whereas group 2 tumours showed marked regression 3-4 weeks after discontinuing CsA. Tumours in group 1 were significantly larger and had greater mitotic activity and showed more ciliary body, optic nerve and extrascleral invasion than tumours in group 2, which showed massive fibrosis, minimal mitotic activity and marked inflammatory cell infiltration. Continuous immunosuppression with CsA seems to be necessary to maintain tumour growth in this experimental model of uveal melanoma.
Subject(s)
Cyclosporine/pharmacology , Immunosuppressive Agents/pharmacology , Melanoma/immunology , Neoplasms, Experimental , Uveal Neoplasms/immunology , Animals , Body Weight/drug effects , Disease Models, Animal , Humans , Male , Melanoma/drug therapy , Mitosis , Rabbits , Time Factors , Tumor Cells, Cultured , Uvea/drug effects , Uvea/pathology , Uveal Neoplasms/drug therapyABSTRACT
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.
Subject(s)
Cyclosporine/administration & dosage , Immunosuppressive Agents/administration & dosage , Lung Neoplasms/secondary , Melanoma, Experimental/secondary , Uveal Neoplasms/pathology , Alanine Transaminase/blood , Animals , Blood Urea Nitrogen , Body Weight , Creatinine/blood , Cyclosporine/pharmacokinetics , Cyclosporine/toxicity , Follow-Up Studies , Immunosuppression Therapy , Immunosuppressive Agents/pharmacokinetics , Immunosuppressive Agents/toxicity , Kidney/drug effects , Lung Neoplasms/drug therapy , Lung Neoplasms/mortality , Male , Melanoma, Experimental/drug therapy , Melanoma, Experimental/mortality , Rabbits , Survival Rate , Tumor Cells, Cultured , Uveal Neoplasms/drug therapy , Uveal Neoplasms/mortalityABSTRACT
CASE REPORT: A case of a 41-year-old woman diagnosed and treated six years ago for a ductal breast carcinoma is presented. The patient complained of blurred vision in the right eye and this symptom was the first manifestation of tumoral relapse. DISCUSSION: We emphasize a correct ophthalmological exploration of cancer patients for an early diagnosis of tumoral spread or relapse. This will allow a proper treatment which is expected to increase the life expectation of these patients.
