Improved efficacy of a microencapsulated macrophage colony stimulating factor and methotrexate in melanoma.
This study examines the effects of a combination therapy of both methotrexate (MTX) and albumin microspheres containing recombinant human macrophage colony-stimulating factor (rhM-CSF) in melanoma tumors. Melanoma tumors were induced in C57BL/6 male mice with subcutaneous injection of B-16 tumor cells. Therapy started once the tumor size reached 0.5 cm in diameter. Mice were divided into several groups, and dosing was carried out daily until death. Group I received MTX solution (2 mg/kg or 15 mg/kg), group II received rhM-CSF solution (100 micrograms), group III received albumin rhM-CSF microspheres (100 micrograms), and groups V-XV received different combinations of both agents daily. The weight, tumor size, and survival time (in days) were recorded. From the results, the control (no rhM-CSF administered) group survived for 11.8 +/- 1.92 days, and the group that received MTX solution survived for 19.4 +/- 5.03 days. However, the group that received both the MTX solution (15 mg/kg) and albumin rhM-CSF microspheres (100 micrograms/kg) demonstrated a significant increase (p < .05) in the survival time (30.4 +/- 3.27 days). The concentrations of cytokines (tumor necrosis factor alpha [TNF-alpha] and interleukin-1 beta [IL-1 beta]) in the different treatment groups were monitored to determine the effect of rhM-CSF on the immune system. The TNF-alpha concentration was significantly higher in the group that received the combination therapy (204 +/- 54.6 pg/ml) versus the control group (31.5 +/- 7.02 pg/ml). The IL-1 beta concentration was significantly higher (p < .05) in the rhM-CSF microsphere (100 micrograms/kg) treated group (62 +/- 17.2 pg/ml) versus the rhM-CSF solution (29.1 +/- 8.7 pg/cc).
D'Souza
M J
MJ
Mercer University, Southern School of Pharmacy, Department of Pharmaceutical Sciences, Atlanta, Georgia 30341, USA.
Pourfarzib
R
R
D000818:Animals; D006801:Humans; D007375:Interleukin-1 / Q000097:blood; D016173:Macrophage Colony-Stimulating Factor / Q000008:administration & dosage*; D008297:Male; D008546:Melanoma, Experimental / Q000188:drug therapy*; D008727:Methotrexate / Q000008:administration & dosage*; D051379:Mice; D008810:Mice, Inbred C57BL; D008863:Microspheres; D011994:Recombinant Proteins / Q000008:administration & dosage; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D007375:Interleukin-1; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016173:Macrophage Colony-Stimulating Factor; D008727:Methotrexate