| Objective To investigate the expression changes of serum inflammatory factors in the patients with soft tissue sarcomas after ablation by retrospective analysis of clinical data and animal experimental study,and analyze their clinical significance on prognosis.Methods The first part: Correlation analysis of the expression of serum inflammatory factors and prognostic indicators in patients with soft tissue sarcomas after ablation.Retrospective analysis was performed on 40 Patients with soft tissue sarcomas who underwent the ablation treatment from December 1st,2016 to December 31 th,2018.They were all treated at the fifth medical center of Chinese PLA general hospital,with complete clinical data.Among them,the serum was retained in 30 patients with soft tissue sarcomas before and after the ablation,and the rest were not retained after the treatment.Enzyme-linked immunosorbent assay(ELISA)was used to detect the expression levels of cytokines IL-1?,IL-6,IL-10,TGF-? and VEGF in the serum of patients and analyze its relationship with the clinical characteristic factors and the prognosis indicators of patients.The second part: Experimental study on the expression changes of the inflammatory factors in the serum of tumor-bearing mice treated with HIFU.BALB/c mice were subcutaneously injected with the human fibrosarcoma cell(HT-1080)to construct mouse fibrosarcoma model.High intensity focused ultrasound ablation(HIFU)was performed on the tumor-bearing mice when the maximum diameter of the tumor reached 7-10 mm.These mice were randomly divided into the normal mice(A)group,tumor-bearing mice+HIFU treatment(B)group and tumor-bearing mice+sham irradiation(C)group.Sham irradiation group,that is,the tumor-bearing mice were exposed to the high intensity focused ultrasound but kept the power source switch of the apparatus off.At about 9am everyday,the vital signs of mice in each group were observed and recorded,and the survival curves of different groups were drawn to monitor the progress ion of the residual tumors.The maximum diameters of the tumor were measured with a ruler and recorded for 30 days.To analyze if there were differences in the changes of the average body weight of each group,the maximum diameters and the volume of tumors in the tumor-bearing mice group.1d before treatment and 1d,7d,14 d,28d after treatment,the eyeballs of the mice were removed for blood collection,centrifugation and serum collection.ELISA was used for detecting the changes of the inflammatory cytokines IL-1?,IL-6 and IL-10 in the serum of the tumor-bearing mice at different periods before and after HIFU treatment,and preliminary analyze the relevant mechanisms.Pearson correlation analysis was performed on the dynamic changes of the tumor maximum diameter and maximum cross-sectional area of the tumor-bearing mice in group B with the expression levels of IL-1?,IL-6 and IL-10 on 1 day before ablation and 1,7,14 and 28 days after ablation.Results The first part: Correlation analysis of the expression of serum inflammatory factors and prognostic indicators in patients with soft tissue sarcomas after ablation.(1)There was no significant difference in the expression levels of IL-1?,IL-6,IL-10,TGF-? and VEGF in the serum of 40 patients with soft tissue sarcoma between different genders,ages,tumor pathological grades and combined therapy was used whether or not(P>0.05).There was a significance in the groups of different maximum diameters(greater or less than 5cm),stage(stage ?+? and stage ?+?)and distant metastasis(whether or not).(1)Between the patients with the maximum diameters of greater than 5cm and the patients with the maximum diameters of less than 5cm,the expression levels of serum IL-1? and IL-10 in the former were higher than those in the latter,and there was a significant difference between these two groups(P<0.05).(2)In different clinical stage,the expression levels of IL-1?,IL-6 and VEGF showed a significant difference between the ?+? stage group and ?+? stage group(P<0.05);(3)The expression levels of IL-1?,IL-6,TGF-? and VEGF were significantly higher in the patients with distant metastasis than those without distant metastasis(P<0.05).(2)Univariate analysis and multivariate Cox regression analysis indicated that the maximum diameter,clinical stage and pathological grade of tumors were important factors which can affect the overall survival of patients.And the tumor pathological grade was an independent factor.(3)The changes of serum inflammatory cytokines and their co rrelation with prognostic indicators of 30 patients with soft tissue sarcoma showed that :(1)The expression levels of IL-1?,IL-6 and TGF-? in the serum were significantly decreased one week after ablation treatment(P<0.05),while the expression levels of IL-10 and VEGF were only slightly reduced(P>0.05).(2)Correlation analysis between the expression level of inflammatory cytokines and overall survival(OS)revealed that the expression level of IL-1? was negatively correlated with OS after ablation(r=-0.483,P=0.007),and the expression level of IL-10 was positively correlated with OS(r=0.419,P=0.021).(3)Correlation analysis between inflammatory cytokine expression level and the PFS indicated that the expression levels of IL-1?,IL-6,IL-10,TGF-? and VEGF after ablation were independent of the PFS(P>0.05).(4)Correlation analysis between the absolute value of the difference in the expression level of inflammatory factors after ablation and OS showed that the expression levels of IL-1? before and after ablation(r=-0.454,P=0.039)and IL-6(r=-0.460,P=0.031)were negatively correlated with OS(-1<r<0,P<0.05),that is,when the expression levels of IL-1? or IL-6 before and after the ablation were increased,the survival time of patients would be shortened.(5)Correlation analysis between the absolute value of the difference in the expression level of inflammatory factors after ablation and the PFS showed that t he expression levels of VEGF before and after ablation was positively correlated with the PFS(r=0.408,P=0.043),that is,when the expression levels of VEGF increased before and after ablation,the PFS of patients also increased.The second part: Experimental study on the expression changes of the inflammatory factors in the serum of the tumor-bearing mice treated with HIFU.(1)The average weight of normal mice in group A kept increasing;The tumor volume of the tumor-bearing mice in group B decreased gradually.After the ablation,the average body weight of the mice in group B decreased firstly,and dropped to the lowest value on the 5 day and then began to increase.The average body weight of the tumor-bearing mice in group C continued to decrease and their tumor volume continued to increase after the sham irradiation.(2)The expression levels of serum inflammatory factors IL-1?,IL-6,IL-10 in the tumor-bearing mice of group B and group C were significantly higher than those in the normal mice of group A.After the HIFU ablation,the expression levels of serum IL-1?,IL-6,IL-10 in the tumor-bearing mice of group B showed a trend of increasing firstly and then decreasing.The highest level of IL-1? was reached on the 7 day after the treatment(61.50±9.06 pg/ml),and the highest level of IL-6 was reached on the 1 day after the treatment(70.70±3.16 pg/ml),and then the expression level began to decrease.The level of IL-10 was up to the maximum at 2 weeks after the HIFU treatment(33.80±3.91 pg/ml),and significantly increased at 1 and 2 weeks after the ablation compared with that before treatment(P<0.05).(3)After the HIFU treatment of the tumor-bearing mice in group B,the maximum tumor sectional area and maximum diameter were not significantly correlated with the dynamic changes of the serum inflammatory factors IL-1?,IL-6 and IL-10.Conclusion The expression levels of serum inflammatory cytokines in the tumorbearing mice were significantly higher than those in the normal mice.After ablation,the expression levels of serum inflammatory cytokines showed a trend of transient increase followed by decrease,and the peak time of different inflammatory cytokines was different.The expression levels of some serum inflammatory factors in the patients with soft tissue sarcomas were significantly different in different tumor diameters and clinical stages.The ablation can down-regulate the expression of some related inflammatory factors.The expression of serum inflammatory cytokines after ablation was correlated with the overall survival and the progression free survival. |
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