Gene therapy for the treatment of chondrosarcoma

利用细胞培养和独创的实验动物模型，在体外和体内研究了基因治疗软骨肉瘤的方法。细胞培养研究表明，加入抗病毒药物（更昔洛韦）后，合并自杀基因（单纯疱疹病毒胸苷激酶基因）的软骨肉瘤细胞具有细胞杀伤作用。以1:50的比例也证实了旁观者效应。软骨肉瘤细胞中的旁观者效应似乎是由间隙连接结构的存在引起的，这在电子显微镜下得到了证实。这些作用通过添加一些细胞杀伤细胞因子TRAIL和TNF α而增强。细胞凋亡导致细胞死亡。皮下注射自杀基因，再腹腔注射抗病毒药物，可明显抑制小鼠肿瘤的生长。自杀基因和抗病毒药物治疗4周后肿瘤大小为对照组的1 / 5。这些结果表明，通过自杀基因治疗软骨肉瘤是有效的治疗方法，除了手术没有有效的治疗方法。通过基因治疗提高软骨肉瘤的生存率，对其他恶性骨和软组织肉瘤的生存率有一定的促进作用。

Gene therapy for the treatment of chondrosarcoma was studied in vitro and in vivo using cell culture and an experimental animal model developed originally. Cell culture study showed cytocidal effect of chondrosarcoma cells incorporated suicide gene (thymidine kinase gene of herpes simplex virus) by addition of anti-virus agent (Ganciclovir). The bystander effect was also confirmed with the ratio of 1:50. The bystander effect in chondrosarcoma cells seems to be caused by the presence of the structure as gap junction which was demonstrated electron microscopically. These effects were enhanced by the addition of some cytocidal cytokines TRAIL and TNF α. Cell death was caused by apoptosis.Growth of the tumor implanted into the mice subcutaneously was markedly inhibited by injection of suicide gene into the tumor and thereafter intraabdominal administration of anti-virus agent. The tumor size after administration of suicide gene and anti-virus agent was one fifth of control after 4 weeks.These results suggest that gene therapy by suicide gene is useful for the treatment of chondrosarcoma which does not have effective treatments except surgery. Improvement of survival rate in chondrosarcoma by gene therapy will contribute to those in other malignant bone and soft tissue sarcomas.