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动脉灌注GE7系统介导Ⅰ型单纯疱疹病毒胸腺嘧啶核苷激酶基因导入大鼠卵巢癌细胞
  • ISSN号:0253-3766
  • 期刊名称:《中华肿瘤杂志》
  • 时间:0
  • 分类:R737.31[医药卫生—肿瘤;医药卫生—临床医学]
  • 作者机构:[1]复旦大学附属妇产科医院妇科,上海 200011, [2]复旦大学附属肿瘤医院乳腺外科, [3]复旦大学实验动物部, [4]上海市肿瘤研究所
  • 相关基金:基金项目:国家自然科学基金(39800144);上海市科技启明星计划基金(01QB14009)
中文摘要:

目的 采用大鼠诱发性卵巢癌模型,观察经肿瘤动脉灌注结合GE7导入系统对Ⅰ型单纯疱疹病毒胸腺嘧啶核苷激酶基因(HSV1-tk)转导的效率和靶向性.方法 构建GE7四元复合物,将诱发的荷瘤大鼠9只随机分成A组、B组和C组,A组经卵巢动脉注入四元复合物(8μg/只),B组注入同体积生理盐水,C组经尾静脉注入四元复合物(8μg/只).给药72 h后,分别以逆转录聚合酶链反应(RT-PCR)和Western blot检测大鼠的肿瘤、心、肝、脾、肺及肾脏组织的HSV1-tk mRNA及蛋白的表达.结果 A组肿瘤组织中HSV1-tk mRNA和蛋白均高表达,而其他组织中则无表达或表达极少 B组未见HSV1-tk mRNA及蛋白的表达 C组肿瘤组织中未见HSV1-tkmRNA和蛋白的表达,肝脏、脾脏、肺脏及肾脏组织中则有少量的表达.RT-PCR半定量检测结果显示,A组卵巢肿瘤组织中的HSV1-tk mRNA含量(1.692±0.221)明显高于C组卵巢肿瘤组织(0.012±0.002 P〈0.01).结论 动脉灌注结合GE7导入系统对HSV1-tk有较高的转导率和靶向性,为HSV1-tk/GCV治疗系统在卵巢癌基因治疗的应用提供了新的策略.

英文摘要:

Objective To observe the gene and protein expression of herpes simplex virus type Ⅰ thymidine kinase (HSV1-tk) in the ovarian tumor tissues and other organs after arterial infusion of HSV1-tk gene mediated by GE7 delivery system.Methods GE7-polylysine/pCMV-HSV1-tk/polylysine-HA20complexes were constructed.Nine rats with induced ovarian tumor were divided into 3 groups, injecting the 4-element complexes or saline buffer through the ovarian artery and complexes through the tail vein,respectively.The ovarian tumors, hearts, livers, spleens, lungs and kidneys were obtained at 72 hours after injection.RT-PCR and Western Blot were preceeded to determine the expression of HSV1-tk gene and protein in the tumor tissues and other organs.Results In the group of arterial injection with 4-element complexes, the HSV1-tk gene and protein were expressed strongly in the tumor tissues, while little or none was detected in other organs.In the group of arterial injection with saline buffer, no HSV1-tk gene and protein was detected in both tumor tissues and other organs.In the group of tail vein injection, none was detected in tumor tissues and only little was found in the livers, spleens, lungs and kidneys.Conclusion High target and gene transfer rates can be obtained when HSV1-tk gene is transferred via the artery route mediated by GE7 delivery system.HSV1-tk protein can be expressed after the gene transfer.The results may provide a new strategy for target killing of HSV1-tk/GCV system in ovarian tumors.

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期刊信息
  • 《中华肿瘤杂志》
  • 北大核心期刊(2011版)
  • 主管单位:中国科协
  • 主办单位:中华医学会
  • 主编:
  • 地址:北京市朝阳区潘家园17号
  • 邮编:100021
  • 邮箱:zhoonghuazhongliu@163@com
  • 电话:010-67788231
  • 国际标准刊号:ISSN:0253-3766
  • 国内统一刊号:ISSN:11-2152/R
  • 邮发代号:2-47
  • 获奖情况:
  • 科协优秀期刊二等奖,首届国家期刊奖提名奖,中国期刊方阵双奖期刊
  • 国内外数据库收录:
  • 美国化学文摘(网络版),荷兰文摘与引文数据库,荷兰医学文摘,美国生物医学检索系统,美国生物科学数据库,日本日本科学技术振兴机构数据库,中国中国科技核心期刊,中国北大核心期刊(2004版),中国北大核心期刊(2008版),中国北大核心期刊(2011版),中国北大核心期刊(2014版),中国北大核心期刊(2000版)
  • 被引量:43252