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在癌肿基因疗法中,作者的实验室已成功地将人体IL-1β(hIL-1β)编码的合成基因插入病毒疫苗(vMJ60hIL-1β),用于感染各种肿瘤细胞,使后者能分泌大量生物活性的hIL-1β,静脉注射后可见hIL-β持续存在和表达至少9天之久.从而出现明显的抑制肿瘤生长现象.为了进一步阐明其抑制胰腺肿瘤的机制,选用C57BL/6鼠进行实验,肿瘤细胞采自PANO2甲基胆蒽诱发的鼠胰腺肿瘤细胞系,每组10只鼠,在皮下注射10~6PANO2细胞后9天,均可扪及肿瘤,随机分别经静脉或肿瘤内注人1×10~5PFUJvMJ60lhIL-1β(以下简称基因疫苗)、1×10~5PFU野生型病毒疫苗或盐水,进行对比.另作重组hIL-1β蛋白实验,对比静脉注射与盐水的效果,观察肿瘤的大小和毒性反应.结果 (一)肿瘤内注射基因疫苗的效果 基因治疗组见肿瘤明显缩小(P<0.01),肿瘤内注射1次基因疫苗,第6天就见肿瘤些微生长,而野生型疫苗和盐水对照组动物的肿瘤持续生长.(二)基因疫苗静脉内或肿瘤内注射的对比 基因疫苗无论经静脉或直接住入肿瘤内,肿瘤生长的抑制程度相似.盐水对照组的肿瘤生长明显较大.静脉内注入重组病毒疫苗可运送克隆基因至肿瘤组织,其效果与基因疫苗直
In cancer gene therapy, the author’s laboratory has successfully inserted the human IL-1β (hIL-1β)-encoded synthetic gene into a viral vaccine (vMJ60 hIL-1β) to infect various tumor cells so that the latter can secrete A large number of biologically active hIL-1β, hIL-β persisted after intravenous injection and expressed for at least 9 days. As a result, tumor growth was significantly inhibited. To further elucidate the mechanism of its inhibition of pancreatic tumors, C57BL/6 mice were used. In the experiment, tumor cells were collected from a pancreatic tumor cell line induced by PANO2 methylcholanthrene, and 10 mice in each group were allowed to invade the tumor 9 days after subcutaneous injection of 10~6PANO2 cells. The tumors were randomly injected intravenously or intratumorally. Humans 1×10~5PFUJvMJ60lhIL-1β (hereinafter referred to as gene vaccine), 1×10~5PFU wild-type virus vaccine or saline were compared. In addition, recombinant hIL-1β protein experiment was conducted to compare the effect of intravenous injection with saline to observe tumors. Size and Toxicity Reactions. Results (I) Effect of Gene Vaccine Injection in Tumors The tumors in the gene therapy group were significantly reduced (P<0.01). Intratumor injection of the gene vaccine was performed. On the 6th day, the tumors showed slight growth, while the wild-type vaccine was used. And saline control animals Tumors continued to grow. (B) Gene vaccines Intravenous or intratumoral injections of comparative gene vaccines The tumor growth was similarly suppressed whether in the vein or directly into the tumor. The saline control group had significantly larger tumor growth. Intravenous injection of recombinant Viral vaccine can deliver cloned genes to tumor tissues, with the effect of genetic vaccines straight