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舒尼替尼对裸鼠肾癌个性化治疗的实验研究(1)
http://www.100md.com 2012年7月5日 《中国医药导报》 2012年第19期
     [摘要] 目的 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。 方法 建立裸鼠背部皮下人肾癌移植瘤模型,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,各组内设给药组与对照组。分别于药后第5、20天及自然死亡后穿刺取活检测定瘤组织中VEGFR-3、PDGFRα表达强度的变化,记录生存时间。 结果 各给药组之间生存时间的差别有统计学意义(F = 32.58,P < 0.001),VEGFR-3、PDGFRα表达强度呈下降趋势。 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。

    [关键词] 舒尼替尼;裸鼠;肾癌;个性化治疗

    [中图分类号] R737.11 [文献标识码] A [文章编号] 1673-7210(2012)07(a)-0031-02
, 百拇医药
    The experiments of Sunitinib personalized treatment for nude mouse kidney cancer

    SUN Feida WANG Dongwen BAI Tao RU Feng ZHANG Xuefeng

    Department of Urology, the First Hospital of Shanxi Medical University, Shanxi Province, Taiyuan 030001, China

    [Abstract] Objective To explicit the expression of vascular endothelial growth factor receptor (VEGFR) and platelet derivative factor receptor (PDGFR) in the kidney cancer, and to understand Sunitinib for individual and resistance of the production process. Methods Models of human renal cell carcinoma transplanted subcutaneously were established, according to the expressed VEGFR and PDGFR, which was divided into VEGFR positive group, PDGFR positive group, VEGFR and PDGFR both positive group, the double negative group, and the team was further divided into treatment group and control group. The expression and change level of VEGFR-3 and PDGFR α were observed after the treatment in 5th days, 20th days and natural death piercing taking biopsy in determination tumor tissue, respectively, the survival time was recorded. Results The differents between the survival times of the four positive group had statistic meanings (=32.58,<0.001). The trend of the expressing level of VEGFR-3 and PDGFRα was drawing. Conclusion Sunitinib can prolong the oerall surial of tumor-burdened nude mouse which expressses VEGFR-3 and PDGFRα, and it has certain directive significance in personalized treatment for kidney cancer.
, 百拇医药
    [Key words] Sunitinib; Node mouse; Kidney cancer; Personalized treatment

    肾癌(renal cell carcinoma,RCC)是泌尿系统常见肿瘤,近年来发病率逐步增加,且发病年龄有年轻化的趋势。RCC是血管最丰富的实体瘤之一[1],肿瘤的生长和转移离不开新生血管提供充的营养及氧供,所以肿瘤血管靶向治疗已逐步发展成为当今肿瘤研究领域的主攻方向之一。舒尼替尼作为唯一突破晚期肾癌2年生存率的药物,通过抑制VEGFR1、VEGFR2、VEGFR3,PDGFRα、PDGFRβ等多种酪氨酸激酶,阻断肿瘤生长所需的血液和营养物质供给,具有抗肿瘤和抗血管生成作用[2-3]。既能直接攻击肿瘤、又无常规化疗的毒副作用,其临床优势是显而易见的。但不同地区和人群对药物的治疗反应也不尽相同,临床应用具有一定的盲目性。所以,寻找舒尼替尼的适宜个体,制订个性化治疗方案,使靶向治疗更具针对性,是本研究着重解决的问题。

    1 材料与方法

    1.1 材料

    雄性BALB/C裸鼠(许可证编号:SCXK京2009-0004)42只,4~6周龄,体重18~22 g,购自中科院北京实验动物中心;人肾透明细胞癌786-O细胞,购自中国科学院上海细胞库;胎牛血清购自美国HyClone公司;苹果酸舒尼替尼(CAS:557795-19-4)购自辉瑞公司;免疫组化试剂盒兔抗人多克隆抗体VEGFR-3(11506B09)、兔抗人多克隆抗体PDGFRα(11961710)购自北京中杉金桥生物技术有限公司。, http://www.100md.com(孙飞达 王东文 白淘 茹峰 张雪峰)
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