Wu Ning, Jin Shun-Zi, Pan Xue-Na, Liu Shu-Zheng
Immunology Laboratory, MH Radiobiology Research Unit, Jilin University School of Public Health, Changchun, China.
Int J Radiat Biol. 2008 Mar;84(3):201-10. doi: 10.1080/09553000801902133.
Design of cancer radiotherapy protocol to reduce radiation dose and increase treatment efficacy in Lewis lung cancer (LLC) model.
C57BL/6J mice subcutaneously implanted with LLC were treated by conventional radiotherapy (2Gy x 6) combined with LDWBI (low dose whole-body irradiation; the second, third, fifth and sixth local doses of 2Gy each substituted by LDWBI with 0.075Gy) and/or gene therapy (intratumor injection of pEgr-IL-18-B7.1 plasmid 24 h before the first and fourth local doses). Immunologic mechanisms were explored.
Cancer control was most significantly improved in the group receiving local radiotherapy combined with LDWBI and gene therapy as shown by prolongation of mean survival time by 60.4%, reduction in average tumor weight by 70.8%, decrease in pulmonary metastasis by 66.9% and decrease in intratumor angiogenesis by 64.8% as compared to local radiotherapy alone (p < 0.05). These changes in tumor growth and progression were accompanied with up-regulation of host immunity manifested by stimulated NK (natural killer) and CTL (cytotoxic T lymphocyte) activity, IFN (interferon)-gamma and TNF (tumor necrosis factor)-alpha secretion, PKC (protein kinase C)-theta activation and LAMP (lysosomal associated membrane protein)-1 expression.
Combination of conventional radiotherapy with LDWBI and gene transfer could reduce total radiation dose by 2/3 and at the same time improve treatment efficacy of cancer accompanied with up-regulated host anticancer immunity.
设计癌症放射治疗方案，以降低Lewis肺癌（LLC）模型中的辐射剂量并提高治疗效果。
对皮下植入LLC的C57BL/6J小鼠进行常规放疗（2Gy×6），联合低剂量全身照射（LDWBI；第二、三、五和六次局部剂量各2Gy分别用0.075Gy的LDWBI替代）和/或基因治疗（在第一次和第四次局部剂量前24小时瘤内注射pEgr-IL-18-B7.1质粒）。探索免疫机制。
与单纯局部放疗相比，接受局部放疗联合LDWBI和基因治疗的组癌症控制得到最显著改善，表现为平均生存时间延长60.4%，平均肿瘤重量降低70.8%，肺转移减少66.9%，瘤内血管生成减少64.8%（p<0.05）。肿瘤生长和进展的这些变化伴随着宿主免疫的上调，表现为自然杀伤（NK）细胞和细胞毒性T淋巴细胞（CTL）活性增强、干扰素（IFN）-γ和肿瘤坏死因子（TNF）-α分泌增加、蛋白激酶C（PKC）-θ激活以及溶酶体相关膜蛋白（LAMP）-1表达上调。
常规放疗与LDWBI及基因转移相结合可将总辐射剂量降低2/3，同时提高癌症治疗效果，并上调宿主抗癌免疫力。
