ABSTRACT
To determine the effects of ibuprofen [Ibp] on the vessel proliferation and necrosis in a rat glioma model. Experimental, randomized interventional trial. 1[st] Neurosurgery Clinic in Bakirkoy Mental Diseases Hospital, Bakirkoy, Istanbul, Turkey, in the year 2010. After stereotactic injection of C6/LacZ rat glioma cells into the Wistar rats brain, the rats were randomly assigned to two treatment groups [group 1, control; group 2, Ibp treatment]. Rats were sacrificed 18 days after treatment, and number of intra-/peri-tumoural vessels, microendothelial proliferations, immunohistochemistry and necrotic area were evaluated. Ibp treatment significantly decreased tumour tissue, intratumoral vessel number and total tumour area level. The level of Ki67 was significantly decreased in the tumour tissue of group 2. Additionally, the total necrotic area / total tumour volume [%] was significantly less in the tumour tissue of the ibuprofen-treated rats compared to the controls. The data show that the Ibp produced an important reduction in glioma tumour cell proliferation in the rat model
ABSTRACT
OBJECTIVE: The aim of the study was to investigate whether lithium chloride and medroxyprogesterone acetate can potentiate the cytotoxicity of imatinib mesylate in human endometrial cancer in vitro and the effect of midkine in these therapies. METHODS: Imatinib mesylate (50 microM), lithium chloride (100 microM), medroxyprogesterone acetate (200 microM) and their combination were applied to monolayer and three dimensional cultures of human Ishikawa endometrial cancer for 72 hours. The cell proliferation index, apoptotic index, caspase-3 and midkine levels, cell cycle distributions in monolayer cultures and cell ultrastructure in spheroid cultures were evaluated. Results were statistically analyzed using the Student's t-test. RESULTS: All drug applications inhibited cell proliferation (p<0.05), however the combination were the effective groups for 72 hours (p<0.05). Interestingly, although the loss of efficiency was seen higly seen every 24 hours at single applications, the inhibition rates of the combination groups were almost same for 72 hours. In concordance with these results, the apoptotic index, caspase-3 levels (p<0.05), cell morphology and ultrastructure damages were much higher in the combination groups. Imatinib mesylate induced S-phase arrest, however other groups induced G0+G1-phase arrest at 24 hours and all groups induced G0+G1 arrest at 72 hours (p<0.05). Imatinib mesylate and imatinib mesylate with medroxyprogesterone acetate induced highest decrease in midkine levels, respectively (p<0.05). CONCLUSION: The present study showed that the combination of imatinib mesylate with lithium chloride and medroxyprogesterone acetate is highly active in Ishikawa endometrial carcinoma in vitro and the inhibition of midkine involved in their mechanism of action against endometrium defense.