INDUCTION OF APOPTOSIS AND REGRESSION OF SPONTANEOUS DOG MELANOMA FOLLOWING IN-VIVO APPLICATION OF SYNTHETIC CYCLIN-DEPENDENT KINASE INHIBITOR OLOMOUCINE

This case report describes a dog with spontaneous melanoma of the orof acial region which was treated by a synthetic inhibitor of cyclin-depe ndent kinases, i.e. olomoucine (OC). The drug was applied i.v. in a si ngle dose of 8 mg/kg/day for 7 days in succession. Repeated bioptic ex aminations of metastatic cervical lymph nodes showed rapid induction o f apoptosis in tumor cells as early as on the third day of treatment. Standard clinical and laboratory examinations did not reveal side effe cts of the therapy. There were no detectable manifestations of myelosu ppression, hepatotoxicity, nephrotoxicity or neurotoxicity. However, t ransient anemia developed following bleeding from a devitalized tumor mass. For this reason, the dog underwent surgery to minimize tumor loa d as well as to eliminate the source of bleeding. Two kilograms of pri mary tumor were extirpated in the course of surgery, including cervica l node metastases. Unfortunately, the dog died soon after surgery due to respiratory depression. Histological examinations of the tumor tiss ue showed marked apoptosis of melanoma cells in both the primary tumor and metastases. The induction of programmed cell death of cancer cell s by OC resulted in rapid eradication of at least 68% of the tumor cel ls. The remaining melanoma cells retained at least equally well in vit ro sensitivity to OC as to drugs currently used in clinical practice.