| Objective To establish a standard subcutaneous bearing tumor nude model with human hepatic tumors which can be imaged with MRI;To study the characteristics of diffusion-weighted imaging(DWI)in nude mice models of hepatic bel-7402 tumors after adenovirus-mediated cytosine diaminase/thymidine kinase (Ad.CD/TK) double suicide gene therapy,and characteristics of apoptosis after therapy,and the relevance of them.Methods We inject Bel-7402 suspension 107/mouse , about 0.2ml subcutaneously in the hip back. 30 nude mice models of hepatic bel-7402 tumors were successfully created,after the tumor grew to more than 1 cm in diameter,21 tumor models were treated by intratumoral administration of Ad.CD/TK for 3 days follow with intraperitonea(i.p.) administration of 5-Fluorocytosine(5-Fc) and Ganciclovir(GCV) for 14 days.Then they were randomly divided into three groups after 5-Fc and GCV treatment.The remaining 9 tumor models were used as controls and randomly assigned to each group.Usual MRI and DWI scanning were performed at different time points (1st day,7th day,14 th day) after 5-Fc and GCV treatment for each group in the 1.5T clinical MR imager with standar small animal coil.Tumor volumes and apparent diffusion coefficient(ADC)values were calculated at different time point.Cell apoptosis were determined by using terminal deoxyuncleotidy transferase Mediated dUTP nick-end-labelling (TUNEL) method.ADC values and the apoptotic index(AI)were calculated using one-way analysis of variance at different times,and two samples t-test were compared between treatment groups and control groups.The correlationship of ADC and apoptotic index were analysed with Pearson-test.Results 30 nude mice models of hepatic bel-7402 tumors were successfully created,there are quite a little differences between tumor sizes.All the tumor masses were investigated with MR imaging techniques,MRI and DWI can be performed with high time and spatial resolution.On the 1st day,7th day,the tumor volumes of the treatment groups and controls were 664.89 mm3 and 573.65 mm3,754.83 mm3 and 833.20mm3 respectively,with no significant difference (P>0.05).On the 14th day,the tumor volumes of the treatment groups and controls were 701.68 mm3 and 1039.46mm3,and a significant difference was observed( P<0.05 ) .On the 1st day,7th day , 14th day , the ADC values of the treatment groups were 0.70±0.04×10-3mm2/s,0.98±0.11×10-3mm2/s,0.93±0.06×10-3mm2/s(F=64.830 ,P<0.01) , the corresponding ADC values of the control groups were 0.70±0.03×10-3mm2/s,0.68±0.04×10-3mm2/s,0.64±0.05×10-3mm2/s , (F=0.936, P>0.05).the ADC values of the treatment groups and control groups were compared,and the t value was -0.278 (P>0.05),4.587 (P<0.01),6.769 (P<0.01).On the 1st day,7th day,14th day,the apoptotic index of the treatment groups were (3.36±1.12)%,(25.11±7.68)%,(23.57±6.23)% (F=31.195 , P<0.01) , the corresponding apoptotic index of the control groups were (2.90±1.22)%,(2.57±0.97)%,(3.10±0.70)% (F=0.224,P>0.05).The apoptotic index of the treatment groups and control groups were compared,and the t value was 0.561 (P>0.05),4.898 (P<0.01),5.485(P<0.01).The ADC values and apoptotic index analysis in the treatment group showed that they were significant positive correlation(r=0.820, P<0.01).Conclusion:Our study results show that subcutaneous tumor of nude mouse model can be successfully created using cell suspension with high rate and almost same sizes.A 1.5T clinical MR imager with standar small animal coil can image with advanced sequences such as DWI for subcutaneous tumor of nude mouse model,with high time and spatial resolution.DWI can reflect the dynamic change at cell apoptosis for hepatic Bel-7402 tumors after Ad.CD/TK therapy at different time quite early before changes of the tumor size. |
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