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目的 观察腺病毒介导白介素 12基因治疗联合放射治疗协同抗小鼠肝癌作用。方法 荷肝癌动物模型 ,肿瘤局部γ射线照射后 ,瘤内注射AdmIL 12腺病毒。取组织标本进行ELISA及CTL活性检测、免疫组化染色等分析。结果 联合治疗小鼠肿瘤生长受到抑制 ,体积明显缩小 ,并可使 5 0 %的小鼠肿瘤完全消退 ,疗效显著优于单纯照射组和瘤内注射AdmIL 12及其他对照组(P <0 0 1)。而单纯瘤内注射AdmIL 12组的疗效并不优于单纯照射组 (P >0 .0 5 )。联合治疗组小鼠血清和脾细胞的培养上清中可见IFN γ水平的显著提高 ,并诱导产生特异性的CTL活性。免疫组化结果显示 ,联合治疗组肿瘤组织中可见有大量CD4+ 、CD8+ 阳性淋巴细胞的浸润。结论 腺病毒介导白介素 12基因治疗与放射治疗的联合具有协同抗肿瘤作用 ,并诱导产生特异性抗肿瘤免疫反应。
Objective To observe the effect of adenovirus-mediated interleukin-12 gene therapy combined with radiation therapy on anti-mouse hepatocarcinoma. Methods The hepatoma-bearing animal model was used to intratumorally inject AdmIL 12 adenovirus after local tumor gamma irradiation. Tissue samples were taken for analysis of ELISA and CTL activity and immunohistochemical staining. Results The tumor growth of mice treated with combination therapy was inhibited, the volume was significantly reduced, and 50% of the mice tumors were completely regressed. The curative effect was significantly better than that of the simple irradiation group and intratumoral injection of AdmIL 12 and other control groups (P <0 01. ). However, the efficacy of intratumoral injection of AdmIL 12 was not better than that of the simple irradiation group (P > 0.05). A significant increase in the level of IFN gamma in the culture supernatant of mouse and spleen cells of the combination treatment group was observed, and specific CTL activity was induced. The results of immunohistochemistry showed that a large number of CD4+ and CD8+ positive lymphocytes were infiltrated in the tumor tissue of the combined treatment group. Conclusion Adenovirus-mediated interleukin 12 gene therapy combined with radiotherapy has a synergistic anti-tumor effect and induces specific anti-tumor immune responses.