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A treatment for metastasis of murine ocular melanoma
1Department of Biology, Queens College, City University of New York, Flushing 11367.
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)
Insights
LS2616 significantly reduced melanoma metastasis in mice when used prophylactically or therapeutically. Pretreatment with LS2616 increased spleen cell activity against B16F10 melanoma cells, suggesting an immune-mediated mechanism.
Area of Science:
- Oncology
- Immunology
- Pharmacology
Background:
- LS2616 demonstrated efficacy in reducing primary tumor growth and pulmonary metastasis of murine melanoma in prior cell culture studies.
- The highly aggressive B16F10 melanoma model in C57BL/6J mice presents a significant challenge for anti-metastatic therapies.
Purpose of the Study:
- To evaluate the prophylactic and therapeutic efficacy of LS2616 against ocular and flank metastases of B16F10 melanoma in vivo.
- To investigate the effect of LS2616 on the immune response against melanoma cells.
Main Methods:
- Mice were treated with LS2616 (160 mg/kg/day) in drinking water.
- Tumor cells were inoculated subcutaneously or intracamerally, with or without drug pretreatment.
- Ocular metastasis models involved enucleation followed by drug treatment.
- In vivo neutralization assays assessed spleen cell activity.
Main Results:
- Prophylactic LS2616 treatment significantly reduced pulmonary metastasis incidence and number.
- Combined pretreatment and enucleation led to reduced lung and lymph node metastasis, increased survival, and a 31% cure rate.
- LS2616 treatment increased spleen cell cytostatic/cytotoxic activity against B16F10 cells.
Conclusions:
- LS2616 demonstrates significant anti-metastatic potential in a highly aggressive melanoma model.
- Prophylactic and peri-enucleation treatment strategies show promising results, including potential for cure.
- LS2616 may exert its effects, in part, through enhancing anti-tumor immune responses.