The Study On Treatment Of Subcutaneous Human Neurogliocytoma Of Nude Mice By High Intensity Focused Ultrasound(HIFU)

Objective:To explore the validity and safety of High Intensity Focused Ultrasound (HIFU) in therapy for neurogliocytoma by observing pathological regression ,the expression of vascular endothelial growth factor and proliferating cell nuclear antigen and the result of apoptosis cell detection in subcutaneous human neurogliocytoma of nude mice after ablation.Methods: This study includede two parts.In the first part ,subcutaneous human neurogliocytoma model of 24 nude mice were established,which were divided into control group and experimental group randomly.An extracorporeal HIFU with 9.7MHz transducer(the focal length of 4.5mm and focal intensity 2500W/cm2) was used.After consecutively ablated by 20s,the growth of subcutaneous human neurogliocytoma was observed in acute stage(≤3d), subacute stage(4~14d) and chronic phase(15~30d); Triphenyl tetrazolium choloride (TTC) staining, HE staining, electron microscope were used. In the second part,the tumor of experimental group in the first part was used to make paraffin section of 5μmtissue. The expression of vascular endothelial growth factor and proliferating cell nuclear antigen was observed by immunohistochemical method and apoptosis cell was detected by the method of TdT-mediated dUTP nick end labeling at exposure coverage, marginal zone and normal zone in 7 days,14 days,30 days after ablation,respectively.Results:All of 24 nude mice were successfully inoculated with SHG-44.After 20 days, subcutaneous human neurogliocytoma was 166.56±9.23 mm3, A statistical difference in tumor volume doubling time(TD)was found between control group and experimental group(p<0.05). Triphenyl tetrazolium choloride (TTC) was used to detect biological focal region(BFR) ,which was 66.12±2.52 mm3.The phenomenon was observed in HE that typical coagulation necrosis was instantly found at exposure coverage after ablation , which was more and more evident ,and marginal zone was examined in subacute stage and chronic phase. There was a clear boundary between the exposure coverage and marginal zone in subacute stage and chronic phase.Typical coagulation necrosis of cell ultramicrostructure was also observed by electron microscope. The expression of vascular endothelial growth factor was observed at exposure coverage, marginal zone and normal zone in 7 days after ablation.There was statistical difference compared with each other(p<0.05). The expression of vascular endothelial growth factor was also observed at marginal zone and normal zone but not exposure coverage in 14 and 30 days after ablation. A statistical difference in positive expression percentage of vascular endothelial growth factor was found between marginal zone and normal zone (p<0.05). There was no expression of proliferating cell nuclear antigen and no apoptosis cell at exposure coverage in 7,14 and 30 days after ablation. A statistical difference in proliferating cell nuclear antigen labeling index and apoptotic index was found between marginal zone and normal zone in 7,14 and 30 days (p<0.05).Conclusion:Under the parameters and dose used in this study,neurogliocytoma at exposure coverage was exactly and soundly ablated.At marginal zone,the proliferation of neurogliocytoma was inhibited.The degraded malignancy degree of neurogliocytoma was also observed at marginal zone.Accordingly,HIFU will be a new and selective way for therapy of neurogliocytoma.