Clinical And Basic Study Of Microwave Ablation For Spinal Metastasis In Breast Cancer

ObjectiveTo investigate the effect of microwave ablation on the proliferation and migration of breast cancer cells,osteogenesis and osteoclast of bone marrow mesenchymal cells at sublethal temperature.Methods1? A retrospective clinical study was conducted in 12 patients with breast cancer with spinal metastases treated by open spine surgery and local microwave ablation from August 2014 to November 2016.The patients were followed up with CT and MRI in January,March and June after the operation,and the local progression and clinical efficacy of the tumors were evaluated with reference to the relevant evaluation indicators.2? A retrospective clinical study was conducted to compare the changes of bone mass before and after partial microwave ablation for the treatment of spinal metastasis in breast cancer.By simulating sublethal temperature on breast cancer cells in vitro,the effects of sublethal temperature on osteoblast and osteoclast of mouse mesenchymal stem cells were compared under different conditions of 37 ?,40 ?,43 ? and 46 ?.3?The expression of MAPK pathway kinase and HSP27 protein in MCF-7cells of breast cancer at sub-lethal temperatures of 37 ?,40 ? and 43 ? were detected by protein immunoblot assay.The expression of osteogenic and osteoclastic genes of bone marrow mesenchymal stem cells was detected by real-time fluorescent quantitative RT-PCR.4?Under the condition of specific blocking of P38-MAPK phosphorylation,the expression of MAPK pathway related kinase and HSP27 protein in MCF-7cells of breast cancer at sub-lethal temperatures of 37 ? and 43 ? were detected by protein immunoblot method,and the expression of osteogenic and osteoclastic genes of bone marrow mesenchymal stem cells was detected by real-time fluorescent quantitative RT-PCR.5?To construct a mouse model of breast cancer cell 4T1 under sublethal conditions of 37 ? and 43 ? in the left ventricle,and compare the tumor formation rate,organ metastasis and bone metastasis of breast cancer cell in the mouse model under the two temperature conditions.ResultThe mean follow-up time for breast cancer patients with thoracic metastases was 10.2 months.The main postoperative complication rate was8.3%,and the local recurrence rate was 16.6%.The local recurrence of spinal metastasis was related to local residual after ablation.Compared with the proliferation of MCF-7 and 4T1 cells at sub-lethal temperatures of 37 ?,40 ?and 43 ?,the proliferation of cells at higher active temperatures in subgroups of MCF-7 and 4T1 cells decreased and the difference was statistically significant(P < 0.05),and all cells of MCF-7 and 4T1 cells died at 46 ?;compared with the migration of cells at higher active temperatures in subgroups of MCF-7 and 4T1 cells,the migration of cells at higher active temperatures in subgroups of MCF-7 and 4T1 was statistically significant(P < 0.05).The effect of MCF-7 cell culture medium on osteogenic and osteoclastic ability of bone marrow mesenchymal stem cells of mice was significant(P < 0.05),and the difference was significant(P < 0.05)when the cells of subgroup acted at lower temperature.The expression of ALP,OCN,BSP and OPG gene of bone marker of bone marrow mesenchymal stem cells induced by conditioned MCF-7culture medium at sublethal temperatures of 37 ?,40 ? and 43 ? increased gradually with the increase of temperature,and the expression of ALP,OCN,BSP and OPG gene at 37 ? vs.40 ? and 37 ? vs.43 ? were compared with statistical significance(P < 0.05).The expression of DCstam,C-SRC,TRAP,MCATK,ATP6,and NFATc1 gene of osteoclasts related markers decreased with the increase of temperature,and the difference was statistical significance(P <0.05).The expression of HSP27 increased with the increase of temperature,compared with 37 ? vs.40 ? and 37 ? vs.43 ?,the difference was statistically significant(P < 0.05).Compared with MAPK pathway related protein expression,the phosphorylation degree of p38-MAPK increased gradually.Under the condition of specific blocking P38-MAPK phosphorylation,the expression of the gene DCstam,C-SRC,TRAP,MCATK,ATP6 VO,and NFATc1 of the sublethal marker MCF-7 was significantly promoted at 43 ?(P< 0.05),and the osteogenesis of mesenchymal stem cells was significantly inhibited at 43 ?(P < 0.05),while the osteoclastic marker gene DCstam,C-SRC,TRAP,MCATK,ATP6 VO,and NFATc1 were inhibited at 43 ?(P <0.05).The inhibition of osteogenesis of mesenchymal stem cells induced by MCF-7 under 43 ? was statistically significant(P < 0.05).The expression of HSP27 was inhibited by MCF-7(P < 0.05).After feeding at 37 ?(control group)and 43 ?(observation group)for 2 weeks,the tumorigenicity of mice decreased,and the difference was statistically significant(P < 0.05)at 37 ? vs.40 ?;the weight of the observation group decreased significantly,and the difference was statistically significant(P < 0.05)at 37 ? vs.40 ?;the incidence of bone metastasis was increased and the difference was statistically significant(P < 0.05);the osteogenesis of local lesions was enhanced and the difference was statistically significant(P < 0.05)ConclusionIncomplete microwave ablation of spinal metastases from breast cancer may lead to phenotypic changes of residual breast cancer cells and the formation of local osteoblastic environment,further induce osteoclast production,p38 MAPK phosphorylation,HSP27 activation participate in the above process,causing local tumor recurrence or metastasis.During clinical treatment,effective physical blockade should be adopted to protect spinal cord nerves,raise local ablation temperature,reduce ablation residue,and further improve the curative effect of microwave local treatment of tumor.