| [Objective] to show the early change of antiangiogenesis and combined with chemotherapy on rabbit VX2soft-tissue tumor model utilizing CT perfusion parameters, tumor morphology and pathology examine, and then to explore the feasibility of volume perfusion CT imaging to dynamically monitor and evaluate the response of antiangiogenic treatment,[methods] To establish an experiment animal model of VX2soft-tissue tumor on40New Zealand white rabbits.40rabbits were randomly divided into4groups, and10rabbits of a group. group1was treated with Endostar alone; group2was treated with Endostar in combination with chemotherapy; group3was treated with chemotherapy alone; group4was control group. Four times of CT volume perfusion scan were performed before treatment and on the second, forth, seventh days of treatment, respectively. The value of blood flow (BF), blood volume (BV), mean transit time (MTT), and permeability (PMB) in the VX2tumor were measured after scanning. Tumor volume was measured on the advanced CT images, and then the values of tumor volume growth and necrosis growth rate were calculated. The microvessel density (MVD) and expression of vascular endothelial growth factor (VEGF) in the tumors were determined with immunohistochemical staining. All statistical analyses were performed by using Statistical software SPSS17.0. Kolmogorov-Smirnov normality test was done. It was impossible to calculate the value of MVD and the expression of VEGF, for there was too less date. The values of the perfusion parameters and tumor growth were compared with Repeated measures ANOVA. P<0.05was consided to be statistically significant.[Ressults] To compare the values among4groups:There is a statistically significant reduction from the control group in the value of tumor volume growth [(1.80±0.45)cm3,(1.08±0.85)cm3] with endostar [(0.89±0.59)cm3,(0.45±0.26)cm3] and with combined therapy [(0.80±0.31)cm3,(0.36±0.15)cm3] on the forth and seventh days of treatment, respectively (P<0.05). There is no significant difference in tumor necrosis growth rate among4groups. On the second and the forth day of treatment, the value of BF in the group with edostar [(78.63±29.71)ml/100ml/min,(82.45±13.17)ml/100ml/min] and combined therapy [(76.51±22.80)ml/100ml/min, (85.58±17.89)ml/100ml/min] was significantly higher than the group with chemotherapy alone [(41.91±11.87)ml/100ml/min,(57.09±15.95) ml/100ml/min] and the control group [(52.61±8.21)ml/100ml/min,(59.89±6.16)ml/100ml/min], respectively (P<0.05); And there is a statistically significant higher from both groups with chemotherapy alone [(48.16±15.63)ml/100ml/min] and control group [(42.04±4.55)ml/100ml/min] in the value of BF with endostar alone [(71.19±12.21) ml/100ml/min] on the seventh day of treatment, respectively (P<0.05). On the second day of treatment, The value of PMB was significantly higher in the endostar group [(70.36±23.46)ml/100ml/min] than both the chemotherapy group [(29.53±12.98) ml/100ml/min] and control group [(27.69±9.45)ml/100ml/min], respectively (P<0.05); On the forth and seventh day of treatment, PMB was as significantly higher in the endostar alone group [(80.33±13.05)ml/100ml/min,(84.76±3.55)ml/100ml/min] and the combined therapy group [(78.12±12.95)ml/100ml/min,(69.83±8.00)ml/100ml/min] than both the group with chemotherapy alone [(47.78±20.09)ml/100ml/min,(39.10±17.50)ml/100ml/min] and the control group [(26.87±6.26)ml/100ml/min,(29.58±11.33)ml/100ml/min]. The values of BV, MTT have no significant difference among4groups. The parameters in one group among different times were compared: in combined therapy group, the value of BF, PMB was higher on the forth day of treatment than the day before treatment. The value of PMB with endostar alone was significantly higher on the second, forth, seventh days of treatment than before the treatment, respectively (P<0.05). However, form the trendgram of mean value of BF, PMB, we can get the result that the increased and reduced range of the mean value of BF, PMB in combined therapy group were higher than in endostar alone group. The mean value of BF, PMB in chemotherapy alone group emerged one time mild increase on the forth day of treatment. MVD of tumor in the chemotherapy alone group and the control group was increased gradually, whereas increased on the second day of treatment and then decreased more in the endostar alone group and the chemotherapy alone group. The VEGF expressions did not differ significantly among4groups.[conclusions] The value of BF, PMB can reflect the change of tumor blood flow and vessel metergasis, and have high sensitivity and accuracy on the aspect of evaluating the early responses of antiangiogenesis; The value of BV, MTT have no significant difference among4groups, therefore, have no evalue to estimate the early responses of combined therapy and antiangiogenic treatment. Tumor growth slowed down but not to shrink after the Endostar and the combined therapy, and the change of tumor growth value was late than the values of BF, PMB. Thus, it was illustrated that tumor morphology cannot make early evaluation promptly to therapeutic effect. There was no significant difference in VEGF expression among4groups and among different times in the one group, it shows that it undesirable to use single angiogenic factors to evaluate the therapy effect. CT perfusion cannot reflect the tumor MVD, but it has superiority in reflecting the tumor perfusion and vascular function. |
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