【摘要】 目的　观察逆转录病毒介导的单纯疱疹病毒胸苷激酶 （HSV TK）、共刺激因子 （B7）基因联合治疗乳腺癌的作用 ,并探讨其作用机理。方法　应用基因重组技术 ,构建携带TK/B7基因的逆转录病毒载体。在 80只SD大鼠乳腺癌模型上 ,分别于瘤体内注射基因转染的乳腺癌细胞 ,3d后腹腔内连续 15d注射更昔洛韦 （GCV） 5 0mg·kg^-1·d^-1。用 4h51Cr释放法检测脾细胞毒T淋巴细胞（CTL）活性。结果　TK组瘤细胞大量凋亡 ;B7组淋巴细胞聚集 ;TK +B7组肿瘤细胞凋亡 ,并可见淋巴细胞的聚集。CTL活性分别为 :对照组 （35 .6± 2 .7） %、TK组 （39.2± 3.8） %、B7组 （6 7.4±4.3） %、TK +B7组 （6 2 .1± 3.5 ） % ,B7、TK +B7组较对照组、TK组显著增强 （P <0 .0 1）。结论　HSV TK、B7联合基因治疗大鼠乳腺癌 ,具有直接杀伤肿瘤和增强机体抗肿瘤免疫双重作用。更多还原

【Abstract】 Objective\ To investigate the therapeutic effects and mechanism of combined gene therapy of retrovirus mediated herpes simplex virus thymidine kinase(HSV-TK) and costimulatory molecule (B7) for murine mammary cancer. Methods\ Gene recombinant technique was used to construct retrovirus vector carrying TK/B7 gene. In the murine mammary cancer model of 80 SD mice, GcTKpSN, GcpB7SN and GcTKpB7SN were injected into the tumor directly and respectively. Three days later, GCV was administered intraperitoneally with a dosage of 50 mg.kg -1 .d -1 for 15 days. The CTL activity of spleen cells were determined by using 4 h 51 Cr releasing method. Results\ Large number of apoptotic cells were found in TK group, lymphocyte infiltration around tumor cells was seen in B7 group and both apoptosis and lymphatic infiltration existed in TK+B7 group. The CTL activity in B7 group (67.4±4.3)% and TK+B7 group (62.1±3.5)% was significantly higher than in in control group (35.6±2.7)% and TK group (39.2±3.8)%. Conclusion\ The combined gene therapy of HSV-TK and B7 for murine mammary cancer could directly kill tumor and enhance immunogenicity.\;更多还原