Treatment with the new ceramide analogs suppresses PEL progression with no visible cytotoxicity in vivo. (A) NOD/SCID mice (6- to 8 week old, male) were injected IP with 12.5, 25, 50 mg/kg of analog 315, 403, or vehicle (n = 5 per group), once daily, 2 days per week, and weights were recorded weekly. The average animal weights after the 4-week treatment period among different groups were compared. (B) At the end of the treatment period, the different organ tissues collected from the representative control, vehicle-, or ceramide analogs– (50 mg/kg) treated mice were observed and compared using the H&E staining (×60 magnification). (C-E) NOD/SCID mice were injected IP with 1 × 10⁷ BCBL-1 cells. Twenty-four hours later, 25 mg/kg of analog 315, 403, or vehicle (n = 5 per group) was administered IP, once daily, 2 days per week, for each of the 2 independent experiments. Weights were recorded weekly. Images of the animals and their spleens as well as ascites fluid volumes were collected at the conclusion of the experiments after the 5-week treatment. Error bars represent SD for 1 of 2 independent experiments; **P < .01. (F) Total ceramide levels of ascites from each of 3 representative vehicle- or ceramide analog–treated mice were quantified using lipidomics analyses as described in the “Methods.” **P < .01. (G) Cell apoptosis in the ascites samples collected from the representative vehicle- or ceramide analog–treated mice was detected using the TUNEL assay (×60 magnification).