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[日本食管癌基因治疗的进展]

[Progress of gene therapy for esophageal cancer in Japan].

作者信息

Matsubara Hisahiro, Ochiai Takenori

机构信息

Department of Academic Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.

出版信息

Gan To Kagaku Ryoho. 2003 Jul;30(7):944-9.

Abstract

Retrovirally expressed interleukin-2 gene, granulocyte macrophage-colony stimulating factor gene, herpes simplex virus-thymidine kinase gene and p53 gene in human esophageal cancer cells showed antitumor effects in a nude mice xenotransplant model. We established a clinical protocol of gene therapy for advanced esophageal cancer using the wild type p53 gene with an adenovirus vector. In December of 2000, we began the first tumor suppressor gene therapy trial. Now, this trial, which has 9 patients. There have been no serious adverse event excluding fever and local pain. The feasibility of this treatment appears fairly good in these 9 cases. Furthermore, we developed a new method for transducing genes without a virus vector since a virus vector has several potentially unwanted properties. In vivo electroporation is a useful strategy for cancer gene therapy. Moreover, electric pulse to established solid tumors increases intracellular concentrations of chemotherapeutic agents. Transduction of the wild-type p53 gene by electroporation decreased the amount of nedaplatin required for tumor suppression. Electrochemo-gene therapy is a relatively simple method and can produce a better therapeutic effect.

摘要

逆转录病毒表达的白细胞介素-2基因、粒细胞巨噬细胞集落刺激因子基因、单纯疱疹病毒胸苷激酶基因和p53基因在人食管癌细胞中,在裸鼠异种移植模型中显示出抗肿瘤作用。我们使用腺病毒载体携带野生型p53基因建立了晚期食管癌基因治疗的临床方案。2000年12月,我们开始了首个肿瘤抑制基因治疗试验。目前,该试验有9名患者。除发热和局部疼痛外,未出现严重不良事件。在这9例病例中,这种治疗方法的可行性看起来相当不错。此外,由于病毒载体有几个潜在的不良特性,我们开发了一种无需病毒载体转导基因的新方法。体内电穿孔是癌症基因治疗的一种有用策略。此外,对已形成的实体瘤施加电脉冲可增加化疗药物的细胞内浓度。通过电穿孔转导野生型p53基因可减少抑制肿瘤所需的奈达铂用量。电化学基因治疗是一种相对简单的方法,能产生更好的治疗效果。

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