舒尼替尼论文：舒尼替尼对裸鼠肾癌干预的实验研究.docVIP

舒尼替尼论文：舒尼替尼对裸鼠肾癌干预的实验研究 【中文摘要】明确血管内皮生长因子受体（VEGFR）及血小板衍生因子受体（PDGFR）在肾癌组织中表达情况，了解舒尼替尼的适用个体，使靶向治疗更有针对性，为临床个性化治疗提供理论依据。方法将肾透明细胞癌786-O细胞培养至对数生长期，胰蛋白酶消化离心后调整细胞浓度至5x107个/ml，注入裸鼠背部皮下，0.1ml/只，2周左右可成瘤。用活检针穿刺取瘤组织，经病理诊断造模成功后用免疫组织化学法检测VEGFR-3、PDGFRα。根据VEGFR-3、PDGFRα是否表达，分为VEGFR阳性组、PDGFR阳性组、双阳组、双阴组，各组内设干预组与对照组。干预组给予舒尼替尼7.5mg/kg/d，对照组给予等体积蒸馏水。分别于干预后第5天、第20天及自然死亡后三次穿刺取活检测定瘤组织中VEGFR-3、PDGFRα表达强度，记录生存时间。结果1.双阴组中的干预组与对照组的生存时间差异无统计学意义（t=1.27，P＝0.25）。双阳组中干预组与对照组的生存时间差异有统计学意义（t=7.01，P＜0.001）；VEGFR阳组中干预组与对照组的生存时间差异有统计学意义（t=2.83，P＝0.02）；PDGFR阳组中干预组与对照组的生存时间差异有统计学意义（t=2.78，P＝0.03），各组中干预组裸鼠生存时间均长于对照组。2.各干预组之间生存时间的差别有统计学意义（F =32.58，P0.001）。双阴组生存时间较双阳组长，双阳组生存时间较VEGFR阳性组长，VEGFR阳性组、PDGFRα阳性组生存时间无明显差别。3.不考虑时间的因素，干预水平（给药与对照）的不同，VEGFR3、PDGFRα表达有差异；不考虑干预的因素，表达强度随时间的变化而减弱；四组时间因素与干预水平均存在交互作用( P均0.05)，随着时间的变化，干预组表达强度减弱幅度大于对照组。结论舒尼替尼可延长VEGFR-3、PDGFRα阳性表达荷瘤裸鼠的总生存期，对肾癌个性化治疗有一定的指导意义。 【英文摘要】In order to clearly nail down the expression of vascular endothelial growth factorreceptor (VEGFR) and platelet derivative factor receptor (PDGFR) in the kidney cancer andadjacent tissues, and to understand sunitinib for individual and resistance of the productionprocess, make targeted therapy more effective,which to provide the theory basis for clinicalpersonalized treatment.Method Prepare 786-O kidney cancer cell culture to logarithmic growth period, then trypsindigestion centrifugal adjusted cell concentration to 5 x107/ ml, and inject it into thesubcutaneous 0.1 ml, after two weeks a tumor form. Make the success of the mould bypathological diagnosis, then use the immunohistochemical method to determine the VEGFR-3and PDGFRαexpression . According to these factors receptor are expressed, which dividedinto VEGFR positive group, PDGFR positive group, VEGFR and PDGFR both positive group,the double negative group, and the team is further divided into treatment group and controlgroup. The treatment group give sunitinib (7.5mg/kg/d), at the same time the control group givevolume distilled water. After the treatment in five d