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Adenovirus-mediated delivery of human IFNgamma gene inhibits prostate cancer growth.

机译:腺病毒介导的人IFNgamma基因递送抑制前列腺癌的生长。

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摘要

Interferon gamma (IFNgamma) is regarded as a potent antitumor agent, but therapy with IFNgamma is hampered by its short half-life and significant side effects. We developed a replication defective adenovirus carrying the human IFNgamma gene and evaluated the effects of adenovirus-mediated IFNgamma (Ad-IFNgamma) gene transfer on human prostate cancer cell lines in vitro and on xenografts in vivo. Our results showed infection of prostate cancer cells with Ad-IFNgamma led to production of an active cytokine and resulted in an antiproliferative effect on the prostate cancer cells. Intratumoral injection of Ad-IFNgamma significantly inhibited the growth of DU-145 cell xenografts in vivo, while no significant toxicity effect was observed. RT-PCR analysis indicated transgene expression mainly enriched in tumors in vivo, and slightly distributed in livers. These findings suggest adenovirus-mediated IFNgamma gene transfer is a promising approach in the treatment of advanced prostate cancer.
机译:干扰素γ(IFNgamma)被认为是有效的抗肿瘤药,但是IFNgamma的半衰期短和明显的副作用阻碍了其治疗。我们开发了携带人IFNgamma基因的复制缺陷型腺病毒,并评估了腺病毒介导的IFNgamma(Ad-IFNgamma)基因转移对人前列腺癌细胞系体外和体内异种移植的影响。我们的结果表明,用Ad-IFNgamma感染前列腺癌细胞会导致活性细胞因子的产生,并导致对前列腺癌细胞的抗增殖作用。肿瘤内注射Ad-IFNγ明显抑制了DU-145细胞异种移植物的体内生长,但未观察到明显的毒性作用。 RT-PCR分析表明转基因表达主要富集于体内肿瘤,并在肝脏中少量分布。这些发现表明,腺病毒介导的IFNγ基因转移是治疗晚期前列腺癌的一种有前途的方法。

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