MRI评价抗肿瘤中药康莱特注射液疗效的实验研究
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摘要
目的评价功能MRI是否能反映肿瘤血管在抗肿瘤治疗前后的变化,并获得MRI相关半定量及定量参数。方法复制结肠癌无胸腺雄性裸鼠BALB/c-nu皮下移植瘤模型,共20只,用中药康莱特注射液对裸鼠进行治疗,监测移植瘤的微血管密度(MVD)、血管内皮生长因子(VEGF)、增殖细胞核抗原(PCNA)等参数,评价疗效和MRI监测结果。应用磁共振弥散加权成像(DWI)扫描,结合药代动力学模型,获得反映肿瘤细胞代谢和微血管通透性的各项半定量及定量参数,评估抗肿瘤治疗的早期疗效;根据药物的体外实验结果选择不同的观测点,分别随机处死一半的载瘤裸鼠,进行免疫组织化学染色。将病理免疫组织化学染色结果与MRI相关半定量及定量参数进行相关性分析。结果中药康莱特注射液作用下的人结肠癌HT-29细胞增殖率下降,比对照组降低33.113%(P<0.05);比对照组HT-29细胞的凋亡率升高28.243%(P<0.05)。表观弥散系数(ADC)ADC_(perf)值、ADC_(3b)及ADC_(10b)与MVD呈正相关(P<0.05)。结论结肠癌裸鼠使用中药康莱特注射液治疗前后,各时期DWI检测获得的定量参数与免疫组织化学法结果有相关性。
Objective To evaluate whether the functional MRI can be used to reflect the change of tumor angiogenesis after drug treatment,and to obtain the related semi-quantitative and quantitative parameters by diffusion magnetic resonance technique.Methods Subcutaneous transplantation model of colorectal cancer was constructed in 20 nude mice.Kanglaite was used for the treatment of colorectal cancer in the nude mice.Microvascular density(MVD),vascular endothelial growth factor(VEGF)and proliferating cell nuclear antigen(PCNA)of the transplanted tumors were monitored.The therapeutic efficiency and MRI monitoring results were evaluated.Combining diffusion magnetic resonance with the pharmacokinetic model,the semi-quantitative and quantitative parameters were obtained,the efficiency of the medicine was evaluated.Half of the nude mice were sacrificed to finish the immunohistochemical staining.The correlations between the pathological findings and the parameters were analyzed.Results After Kanglaite injection treatment,the proliferation rate of human colon cancer HT-29 cells significantly decreased by33.113%compared to the control group(P<0.05).Compared with the control group,the apoptosis rate of HT-29cells increased by 28.243%(P<0.05).The correlation analysis between pathological examination and diffusion magnetic resonance parameters showed that ADC_(perf),ADC_(3b) and ADC_(10b) were positively correlated with MVD(P<0.05).Conclusions The quantitative parameters of diffusion magnetic resonance are closely correlated with immunohistochemical results in Kanglaite treatment of human colon cancer in nude mice.
Objective To evaluate whether the functional MRI can be used to reflect the change of tumor angiogenesis after drug treatment,and to obtain the related semi-quantitative and quantitative parameters by diffusion magnetic resonance technique.Methods Subcutaneous transplantation model of colorectal cancer was constructed in 20 nude mice.Kanglaite was used for the treatment of colorectal cancer in the nude mice.Microvascular density(MVD),vascular endothelial growth factor(VEGF)and proliferating cell nuclear antigen(PCNA)of the transplanted tumors were monitored.The therapeutic efficiency and MRI monitoring results were evaluated.Combining diffusion magnetic resonance with the pharmacokinetic model,the semi-quantitative and quantitative parameters were obtained,the efficiency of the medicine was evaluated.Half of the nude mice were sacrificed to finish the immunohistochemical staining.The correlations between the pathological findings and the parameters were analyzed.Results After Kanglaite injection treatment,the proliferation rate of human colon cancer HT-29 cells significantly decreased by33.113%compared to the control group(P<0.05).Compared with the control group,the apoptosis rate of HT-29cells increased by 28.243%(P<0.05).The correlation analysis between pathological examination and diffusion magnetic resonance parameters showed that ADC_(perf),ADC_(3b) and ADC_(10b) were positively correlated with MVD(P<0.05).Conclusions The quantitative parameters of diffusion magnetic resonance are closely correlated with immunohistochemical results in Kanglaite treatment of human colon cancer in nude mice.
引文
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[10]彭新桂,柏盈盈,居胜红,等.小鼠下肢急性缺血模型的制作及影像评价[J].东南大学学报(医学版),2014(3):254-259.
[11]王飞,王亚非,王以浪,等.康莱特对人结肠癌裸鼠种植瘤肝转移的影响[J].现代肿瘤医学,2011,19(6):1083-1085.
[12]印滇,姚登福,王亚非,等.康莱特抑制结肠癌细胞转移的作用及其分子机制研究[J].胃肠病学和肝病学杂志,2012,21(11):1005-1010.
[2]ZHENG,Q H,WU X L,CHE X L,et al.Chemotherapy combined with target drugs in the treatment of advanced colorectal cancer:a meta-analysis based on Chinese patients[J].Indian J Cancer,2014,51(Suppl 3):DOI:10.4103/0019-509X.154100.
[3]LEUNG D,HAN X,MIKKELSEN T,et al.Role of MRI in primary brain tumor evaluation[J].J Natl Compr Canc Netw,2014,12(11):1561-1568.
[4]LEE J E,KIM C,YANG H,et al.Novel glycosylated VEGF decoy receptor fusion protein,VEGF-Grab,efficiently suppresses tumor angiogenesis and progression[J].Mol Cancer Ther,2015,14(2):470-479.
[5]FU S,BAI R,ZHAO Z,et al.Overexpression of hypoxia-inducible factor-1alpha and vascular endothelial growth factor in sacral giant cell tumors and the correlation with tumor microvessel density[J].Exp Ther Med,2014,8(5):1453-1458.
[6]HONG G,YUAN R,LIANG B,et al.Folate-functionalized polymeric micelle as hepatic carcinoma-targeted,MRIultrasensitive delivery system of antitumor drugs[J].Biomed Microdevices,2008,10(5):693-700.
[7]SUDO S,HATTORI N,MANABE O,et al.FDG PET/CT diagnostic criteria may need adjustment based on MRI to estimate the presurgical risk of extrapelvic infiltration in patients with uterine endometrial cancer[J].Eur J Nucl Med Mol Imaging,2015,42(5):676-684.
[8]王飞,王亚非,王以浪,等.康莱特对人结肠癌裸鼠种植瘤肝转移的影响[J].现代肿瘤医学,2011,19(6):1083-1085.
[9]张金山,罗良平,史长征,等.99Tcm-Annexin V显像联合MRDWI检测125I内照射后肺腺癌裸鼠移植瘤的细胞凋亡[J].中华核医学与分子影像杂志,2014,34(5):385-389.
[10]彭新桂,柏盈盈,居胜红,等.小鼠下肢急性缺血模型的制作及影像评价[J].东南大学学报(医学版),2014(3):254-259.
[11]王飞,王亚非,王以浪,等.康莱特对人结肠癌裸鼠种植瘤肝转移的影响[J].现代肿瘤医学,2011,19(6):1083-1085.
[12]印滇,姚登福,王亚非,等.康莱特抑制结肠癌细胞转移的作用及其分子机制研究[J].胃肠病学和肝病学杂志,2012,21(11):1005-1010.