Serine palmitoyltransferase inhibitor myriocin induces growth inhibition of B16F10 melanoma cells through G(2) /M phase arrest.

OBJECTIVES: Melanoma is the most aggressive form of skin cancer, and it resists chemotherapy. Candidate drugs for effective anti-cancer treatment have been sought from natural resources. Here, we have investigated anti-proliferative activity of myriocin, serine palmitoyltransferase inhibitor, in the de novo sphingolipid pathway, and its mechanism in B16F10 melanoma cells. MATERIAL AND METHODS: We assessed cell population growth by measuring cell numbers, DNA synthesis, cell cycle progression, and expression of cell cycle regulatory proteins. Ceramide, sphingomyelin, sphingosine and sphingosine-1-phosphate levels were analysed by HPLC. RESULTS: Myriocin inhibited proliferation of melanoma cells and induced cell cycle arrest in the G(2) /M phase. Expressions of cdc25C, cyclin B1 and cdc2 were decreased in the cells after exposure to myriocin, while expression of p53 and p21(waf1/cip1) was increased. Levels of ceramide, sphingomyelin, sphingosine and sphingosine-1-phosphate in myriocin-treated cells after 24 h were reduced by approximately 86%, 57%, 75% and 38%, respectively, compared to levels in control cells. CONCLUSIONS: Our results suggest that inhibition of sphingolipid synthesis by myriocin in melanoma cells may inhibit expression of cdc25C or activate expression of p53 and p21(waf1/cip1) , followed by inhibition of cyclin B1 and cdc2, resulting in G(2) /M arrest of the cell cycle and cell population growth inhibition. Thus, modulation of sphingolipid metabolism by myriocin may be a potential target of mechanism-based therapy for this type of skin cancer.

Comparison of frame-based and frameless stereotactic hematoma puncture and subsequent fibrinolytic therapy for the treatment of supratentorial deep seated spontaneous intracerebral hemorrhage.

OBJECTIVE: This study compared the technical implications and clinical outcome of patients treated for an intracerebral hemorrhage using two minimally invasive procedures: frame-based stereotactic hematoma aspiration and frameless navigation-guided hematoma aspiration followed by fibrinolysis. METHODS: Thirty patients with a spontaneous supratentorial intracerebral hemorrhage, which was treated by a frame-based (n=15) and frameless (n=15) hematoma aspiration followed by subsequent fibrinolysis with urokinase, were retrospectively reviewed. The data for the two subsets of patients were analyzed with regard to hematoma reduction, Glasgow Coma Scale (GCS), and degree of weakness. RESULTS: In the frame-based stereotactic hematoma aspiration group, the volume of the hematoma was 15.4-100.0 mL (mean: 40.7+/-24.4), the GCS upon admission was 4-15 (mean: 10.1+/-3.0), and the grade of weakness upon admission was 1-5 (mean: 2.1+/-0.9). On the other hand, in the frameless navigation-guided hematoma aspiration group, the hematoma volume was 15.2-62.0 mL (mean: 30.0+/-15.2), the GCS upon admission was 7-15 (mean: 13.0+/-2.4), and the grade of weakness upon admission was 1-4 (mean: 2.3+/-1.2). The drainage catheter was in place for a mean duration of 5.1+/-2.4 days (range: 1-12 days). In the frame-based group, the initial hematoma was reduced by -115-88.5% (mean: 52+/-31.5) immediately after surgery, and 90.5% (41-100%) of the initial volume 14 days after surgery. In the frameless group, the initial hematoma was reduced by 11.7-90.8% (mean 57.3+/-25.1) immediately after surgery and 95.8% (87.7-100%) 14 days after surgery. The GCS score and the degree of weakness were evaluated 14 days after surgery, and the Glasgow outcome scale (GOS) score was evaluated at discharge. There were no statistically significant differences between the two groups. CONCLUSION: The frame-based group and the frameless group followed by fibrinolysis had similar outcomes, and both procedures effectively reduced the intracerebral hemorrhage volume within a short period of time. In addition, these procedures are simple, precise, safe, and brief with a very low rebleeding rate and mortality.