Experiment Research On TACE Combined With Endostar In The Treatment Of Rabbit VXâ…¡ Hepatic Tumor Model

Objective:To compare the dynamic parameters of pathological tissue andimmunohistochemistry and DWI of rabbit VXⅡ hepatic tumor after transcatheterarterial chemoembolization(TACE)only and TACE combined with endostar. Verifycurative treatment affected of TACE combined with endostar of rabbit VXⅡ livercancer model, To provide research-based treatment of TACE combined with endostarof liver cancer.Materials and Methods：1.1Establishment of rabbit VXⅡ hepatic tumor modelThirty three New Zealand white rabbits provided by Sun yat-sen universitylaboratory animal center And weighing about2.5-3.0kg. Cut open the abdominalcavity and tumor tissue(1-3mm3) biopsy in the left hepatic lobe. Successfully establish30rabbit VXⅡ hepatic tumor models.1.2Magnetic resonance imaging30rabbit VXⅡ liver cancer models were processed MRI scans(T1WI, T2WI,T2WI fat suppression sequences and DWI imaging) before interventional surgery andone week after surgery by Philips1.5T superconductive MRI system. T2WI, T2WI fatsuppression scanning parameters: TR3544ms，TE81ms，FOV l50mm，slice thickness3mm，interlayer spacing1mm，matrix256x256，reconstruction matrix512×512，NSA2times。T1WI scanning parameters：TR407ms，TE17ms，FOV150mm，slicethickness3mm，interlayer spacing1mm，matrix256×256，reconstruction matrix512×512，NSA2times，EL=3。DWI echo planar imaging (EPI) scanning parameters， 0s／mm2and600s／mm2for b value,TR6000ms，TE49ms，FOV150mm，slicethickness3mm，interlayer spacing0mm，matrix112×112，reconstruction matrix256×256，flip angle90°，NSA6times。Rabbit VXⅡ hepatic tumor model DWIimages and ADC images by workstations processed under the b value were got. SetROIs in the liver lesions and normal liver tissue of DWI images.To maintain the samesize ROI using the copy and paste method. Avoid large liver vascular, bile duct andartifacts while measure ADC value. Record ADC values of DWI images when b valueis600sec/mm2.1.3interventional therapyAll rabbit VXⅡ liver cancer models were underwent right femoral arterypuncture and intra-arterial infusion.30rabbit VXⅡ liver cancer models wererandomly divided into three groups(n=10),and different drugs were perfused:groupA,TACE bombined therapy group(pharmorubicin5mg+liquid iodized oil1ml+endostar1mg);group B,TACE group(pharmorubicin5mg+liquid iodized oil1ml);group C,control group(0.9%sodium chloride2ml).1.4pathological tissue and immunohistochemistryOne week after surgery, all rabbits were sacrificed after MRI scans. the tumorand adjacent hepatic tissue were collected and performed with immunohistochemistrystudies for microvessel density(MVD)and vascular endothelial growth factor(VEGF)．1.5Statistical analysisRepeated-measures variance analysis was firstly performedto test whether grouping existed interactive effect and principal effect or not．Inaddition,LSD-t was used to compare the significant differences in pairwisecomparison,and Tamhane was used to compare the significant differences in pairwisecomparison for heterogeneity of variance.T-test was used compare the significantdifferences in pre-therapy and post-therapy.A P value of less than0.05was consideredto indicate a significant difference.Results:2.1MRI and DWI images difference between pre-therapy and post-therapyThe tumors were solitary,round or oval,and expansive growth which have clearboundaries with nearby liver tissue in pre-therapy.T1WI showed low signal,T2WIshowed mid-high signal,signal heterogeneity,and higher signal in central area.The tumors showed high signal in DWI images,low signal heterogeneity in central area.The tumors were signal heterogeneity in T1WI and T2WI.In DWI images,lowsignal showed in central area and slightly high signal in peripheral region.2.2Change of ADC value between pre-therapy and post-therapyIn pre-therapy,the ADC value difference were not statistically significant(p=0.27)in three groups（1.58±0.21、1.61±0.18、1.57±0.24）×10-3.In post-therapy,the ADCvalue of group A and B（2.38±0.15、2.21±0.18）×10-3were higher than that inpre-therapy;the ADC value of group C（1.68±0.16）×10-3were higher than that inpre-therapy，but there was no statistically significant;the ADC value of group A and Bwere higher than group C.the ADC value of group A was higher than group B.2.3Difference of VEGF and MVD values between three groups inpost-therapyIn post-therapy,the VEGF and MVD value difference of three groups werestatistically significant.the VEGF and MVD value of group A was lower than group Band C.Group B was higher than group C.Conclusions:1. The VEGF and MVD value of rabbit VX2hepatic tumor were Significantlyincreased after TACE,which reflected the activity of neovascularization.Thisphenomenon might be explained the increase rate of relapse and metastasis afterTACE for management of HCC.2.The expression of VEGF and MVD of rabbit VX2hepatic tumor significantlydecreased in combined therapy group, ADC values of combination therapy group washigher than TACE group,which demonstrated that endostar might inhibit tumorangiogenesis and therefore improved the therapeutic effects of TACE.