Targeted Gene Therapy for Brain Tumor

纤维突变型E1 B对胶质瘤基因治疗的严重增强细胞学效应（英语：Defective Adenovirus）。Cancer Res，1999.一种E1 B55-kDa基因缺陷腺病毒（Adv），ONYX-015，有报告称它是一种高度有用的复制能力的广告，它显示出癌症对不正常的p53基因的细胞学效应，而不破坏正常的疾病。在这项研究中，我们将这个广告（Adv-E1 Adb）与光纤突变， F/K20结合在一起，我们在光纤的COO-H-终止处添加了20个赖氨酸驻地，并显示出高的转换效率，使之成为胶质细胞。在U-373 MG胶质瘤细胞中，LacZ的Adv-F/K20的转换效率比LacZ的裸型纤维（Adv-F/wt）的Adv高9倍。在30个感染的多个方面，Adv-E1 AdB-F/K20的复制效率比使用wt纤维的Adv-E1 AdB（Adv-E1 AdB-F/wt）高出11次。AdvE 1AdB-F/K20到U-373 MG细胞的ED 50值，它是体外细胞效应的衡量标准，为32次 ... More 大于Adv-E1 AdB-F/wt。吸入Adv-E1 AdB-F/K20抑制体内肿瘤的生长。Adv-E1 AdB-F/K20的反效应比Adv-E1 AdB-F/wt更强。通过感染的Adv-E1 AdB-F/K20在体外和体内演示的复制病毒蛋白（六边形）的较大数量，与Adv-E1 AdB-F/wt进行比较。在整合中，使用Adv-E1 AdB-F/K20进行基因治疗，当从理论上增强Adv-E1 AdB的抗原效应时，将提议将治疗方法应用于胶质瘤。腺病毒介导的p33-D1 ING-D1与p53-D1中的抗原突变。Cancer Res，1999. P53肿瘤抑制剂基因是癌症基因治疗的重要目标，也是临床试验的目标，以确定这种基因已被接受。有些癌症，还有更多的，是p53基因疗法的基础。Therefor，它已与其他疗法结合在一起，包括化学疗法和放射疗法，以增强细胞学效应对p53诱导。p33イD1ING1イD1gene cooperates with p53 to block cell proliferation。在本研究中，我们调查了腺病毒（Adv）介导的p33型D1 ING 1型D1和p53增强胶质瘤细胞（U251和U-373 MG）中的寄生虫，其中显示了无遗传变化但p33型D1 ING 1型D1型表达水平较低。Adv-p33和Adv-MBP-p53在两个细胞线上诱导的相同MOIs在病理上增强了凋亡。我们的结果表明，这种联合感染方法可以被用作胶质瘤基因治疗的一种模式，对正常疾病造成损害。Less（低）

Highly augmented cytopathic effect of a fiber-mutant E1B-defective adenovirus for gene therapy of glioma. Cancer Res., 1999. An E1B 55-kDa gene-defective adenovirus(Adv), ONYX-015, has been reported to be a highly useful replication-competent Adv that shows cytopathic effect for cancers with an abnormal p53 gene, without damaging normal tissues. In this study, we combined this Adv (Adv-E1Adb) with a fiber mutation, F/K20, which has a stretch of 20 lysine residues added at the COO-H-terminus of the fiber and shows high transduction efficiency to gliomas. In U-373 MG glioma cells, the transduction efficiency of Adv-F/K20 for lacZ was nine times higher than that of the Adv with wild-type fiber (Adv-F/wt) for lacZ. At a multiplicity of infection of 30, the replication efficiency of Adv-E1AdB-F/K20 was 11 times higher than that of Adv-E1AdB with wt fiber (Adv-E1AdB-F/wt). The ED50 value of AdvE1AdB-F/K20 to U-373 MG cells, which is a measure of the in vitro cytopathic effect, was 32 times g … More reater than that of Adv-E1AdB-F/wt. Injection of Adv-E1AdB-F/K20 suppressed the in vivo growth of tumors. The antitumoral effect of Adv-E1AdB-F/K20 was remarkably stronger than that of Adv-E1AdB-F/wt. A greater quantity of replicated virus protein (hexon) by infection with Adv-E1AdB-F/K20 was demonstrated in vitro and in vivo, compared with that of Adv-E1AdB-F/wt. In conclusion, gene therapy using Adv-E1AdB-F/K20, which drastically augmented the antitumoral effect of Adv-E1AdB, will be promising therapeutic approach for gliomas.Adenovirus-mediated transfer of p33ィイD1INGィエD1 with p53 drastically augments apoptosis in gliomas. Cancer Res., 1999. The p53 tumor suppressor gene is an important target for the gene therapy of cancers, and clinical trials targeting this gene have been conducted. Some cancers, however, are refractory to p53 gene therapy. Therefor, it has been combined with other therapies including chemotherapy and radiotherapy to enhance the cytopathic effect of p53 induction. The p33ィイD1ING1ィエD1 gene cooperates with p53 to block cell proliferation. In this study, we investigated whether adenovirus (Adv)-mediated co-induction of p33ィイD1ING1ィエD1 and p53 enhances apoptosis in glioma cells (U251 and U-373MG), which showed no genetic alterations but low expression levels of p33ィイD1ING1ィエD1. Co-infection of Adv-p33 and Adv-MBP-p53 at the same MOIs induced drastically enhanced apoptosis in both cell lines. Our results indicated that this co-infection approach can be used as a modality for the gene therapy of gliomas, sparing damage to normal tissues. Less