A treatment for metastasis of murine ocular melanoma

Abstract

In experiments using cultured cells, LS2616 has been shown to decrease growth of primary tumors and pulmonary metastasis of murine melanoma. In the current study, we examine the efficacy of LS2616 for the prophylactic and therapeutic treatment of metastases from ocular and flank inoculations of the highly aggressive in vivo derived B16F10 melanoma in C57BL/6J mice. Experimental animals were treated with 160 mg/kg/day of this drug in drinking water, until they became moribund or died. When mice were pretreated for 7 days and inoculated subcutaneously (sc) or intracamerally (ic) with 10(5) in vivo derived B16F10 tumor cells, the mean number of pulmonary metastases was significantly reduced, and the incidence of pulmonary metastases decreased. In ocular experiments, when pretreatment with drug was combined with enucleation at day 7, the mean number of lung nodules was significantly reduced, the incidence of metastasis to the lung and lymph nodes decreased and survival increased. An apparent cure rate of 31% was observed. Treatment beginning on the day of enucleation (day 7) resulted in a reduction of pulmonary metastases, a decrease in metastasis to the lungs and lymph nodes and no change in survival. LS2616 did not alter tumorigenicity of either sc or ic inoculations. In an in vivo neutralization assay, spleen cells of mice treated for 7 days with LS2616 demonstrated an increase in cytostatic or cytotoxic activity when incubated with B16F10 melanoma cells.(ABSTRACT TRUNCATED AT 250 WORDS)