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原位CD基因转导配合全身应用5-FC对于前列腺癌原位移植瘤模型肿瘤和转移的抑制作用

张正望 殷莲华 张永康 赵凤娣

中华医学杂志(英文版)2002,Vol.115Issue(2):227-231,5.
中华医学杂志(英文版)2002,Vol.115Issue(2):227-231,5.

原位CD基因转导配合全身应用5-FC对于前列腺癌原位移植瘤模型肿瘤和转移的抑制作用

In situ transduction of cytosine deaminase gene followed by systemic use of 5-fluorocytosine inhibits tumor growth and metastasis in orthotopic prostate cancer mouse models

张正望 1殷莲华 2张永康 1赵凤娣2

作者信息

  • 1. 复旦大学医学院(原上海医科大学)附属中山医院泌尿外科,上海,200032
  • 2. 复旦大学医学院病理生理教研室,上海,200032
  • 折叠

摘要

Abstract

Objective To investigate the antitumor and anti-metastatic effect of in situ transduction of adenovirus encoding cytosine deaminase (AdCD) followed by the systemic use of 5-fluorocytosine (5-FC) in the orthotopic (o.t.) prostate cancer mouse model.Methods The o.t. prostate cancer model of C57BL/6 mouse was developed by o.t. inoculation of RM-1 cells to the subcapsular area of the prostate gland. In situ transduction of the CD gene, followed by systemic use of 5-FC at a daily dosage of 300?mg/kg for 14 days, was performed two days later.Results Compared with mice treated with Adβ-gal/5-FC, 5-FC and PBS, mice of the o.t. model receiving in situ treatment of AdCD/5-FC had significant prolongation of survival and suppression of local tumor growth. More importantly, pathological observations showed that metastatic activity occurred in all mice of the PBS, 5-FC and Adβ-gal groups including metastasis to the iliac lymph node (10/10, 10/10, 10/10) and the lung (8/10, 7/10, 7/10). However, only two out of ten had iliac lymphatic metastasis in the AdCD/5-FC group with no systemic or preaotic lymphatic metastasis, suggesting a strong metastatic inhibitory effect.Conclusions In situ transduction of AdCD followed by systemic use of 5-FC leads to the inhibitory effect on tumor growth and metastatic activity in the o.t. mouse model of prostate cancer. Clinically, it may be possible to treat metastatic or recurrent prostate cancer with a novel gene therapy using in situ injection techniques in future.

关键词

胞嘧啶脱胺酶/氟胞嘧啶/基因治疗/前列腺肿瘤/动物

Key words

cytosine deaminase/flucytosine/gene therapy/prostatic neoplasms/animal

分类

医药卫生

引用本文复制引用

张正望,殷莲华,张永康,赵凤娣..原位CD基因转导配合全身应用5-FC对于前列腺癌原位移植瘤模型肿瘤和转移的抑制作用[J].中华医学杂志(英文版),2002,115(2):227-231,5.

中华医学杂志(英文版)

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