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ω-干扰素的抗肿瘤作用:裸鼠体内人肿瘤异种移植瘤的治疗

Antitumor effects of interferon-omega: in vivo therapy of human tumor xenografts in nude mice.

作者信息

Horton H M, Hernandez P, Parker S E, Barnhart K M

机构信息

Vical, Inc., San Diego, California 92121, USA.

出版信息

Cancer Res. 1999 Aug 15;59(16):4064-8.

Abstract

The antitumor effect of the type I IFN, IFN-omega, was evaluated in both in vitro and in vivo studies of human cancer. For these studies, the cDNA for human IFN-omega was cloned into a eukaryotic expression plasmid DNA (pDNA) driven by the cytomegalovirus promoter. Supernatants from UM449 cells transfected in vitro with IFN-omega pDNA had antiproliferative effects on 11 of 13 human tumor cell lines. For in vivo studies, nude mice were implanted s.c. with one of the following human tumors: NIH: OVCAR-3 ovarian carcinoma, A375 melanoma, or A431 epidermoid carcinoma. Direct intratumoral injection of 100 microg of a IFN-omega pDNA DMRIE/DOPE complex (1:1 DNA:DMRIE mass ratio) for 6 consecutive days resulted in a significant reduction in the tumor volume of NIH: OVCAR-3 ovarian carcinoma or A375 melanoma (P = 0.02). IFN-omega pDNA delivered by i.m. injection also had an antitumor effect. Nude mice bearing s.c. A431 epidermoid carcinoma and injected i.m. with 100 microg of IFN-omega pDNA, twice per week for 3 weeks, had a significant reduction in tumor volume (P = 0.009). These results demonstrate for the first time that IFN-omega can have in vivo antitumor effects in several models of human cancer.

摘要

在人癌症的体外和体内研究中评估了I型干扰素ω(IFN-ω)的抗肿瘤作用。对于这些研究,将人IFN-ω的cDNA克隆到由巨细胞病毒启动子驱动的真核表达质粒DNA(pDNA)中。用IFN-ω pDNA体外转染的UM449细胞的上清液对13种人类肿瘤细胞系中的11种具有抗增殖作用。对于体内研究,将裸鼠皮下植入以下人类肿瘤之一:NIH:OVCAR-3卵巢癌、A375黑色素瘤或A431表皮样癌。连续6天直接瘤内注射100μg IFN-ω pDNA DMRIE/DOPE复合物(DNA与DMRIE质量比为1:1)可使NIH:OVCAR-3卵巢癌或A375黑色素瘤的肿瘤体积显著减小(P = 0.02)。肌肉注射递送的IFN-ω pDNA也具有抗肿瘤作用。皮下接种A431表皮样癌并每周两次肌肉注射100μg IFN-ω pDNA,共3周的裸鼠,其肿瘤体积显著减小(P = 0.009)。这些结果首次证明IFN-ω在几种人类癌症模型中可具有体内抗肿瘤作用。

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