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Ras-1激酶抑制因子的药理学失活可消除Ras介导的胰腺癌。

Pharmacologic inactivation of kinase suppressor of ras-1 abrogates Ras-mediated pancreatic cancer.

作者信息

Xing H Rosie, Cordon-Cardo Carlos, Deng Xinzhu, Tong William, Campodonico Luis, Fuks Zvi, Kolesnick Richard

机构信息

Laboratory of Signal Transduction, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, USA.

出版信息

Nat Med. 2003 Oct;9(10):1266-8. doi: 10.1038/nm927. Epub 2003 Sep 7.

DOI:10.1038/nm927
PMID:12960962
Abstract

Inhibition of the kinase suppressor of ras-1 (KSR1) gene by continuous infusion of phosphorothioate antisense oligonucleotides (ODNs) prevented growth of K-Ras-dependent human PANC-1 pancreatic and A549 non-small-cell lung carcinoma xenografts in nude mice, effected regression of established PANC-1 tumors and inhibited A549 lung metastases, all without apparent toxicity. These studies suggest KSR1 antisense ODNs as a treatment for Ras-dependent human malignancies, in particular pancreatic cancer, which lacks effective curative therapy.

摘要

通过持续输注硫代磷酸酯反义寡核苷酸(ODN)抑制ras-1激酶抑制因子(KSR1)基因,可阻止依赖K-Ras的人胰腺癌细胞PANC-1和非小细胞肺癌细胞A549在裸鼠体内异种移植瘤的生长,使已形成的PANC-1肿瘤消退,并抑制A549肺转移,且均无明显毒性。这些研究表明,KSR1反义ODN可作为治疗依赖Ras的人类恶性肿瘤的方法,尤其是胰腺癌,因为目前胰腺癌缺乏有效的治愈性疗法。

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