Pharmacologic inactivation of kinase suppressor of ras-1 abrogates Ras-mediated pancreatic cancer
Pharmacologic inactivation of kinase suppressor of ras-1 abrogates Ras-mediated pancreatic cancer
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DOI：
10.1038/nm927
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发表时间：
2003-10-01
期刊：
影响因子：
82.9
通讯作者：
Kolesnick, R
中科院分区：
文献类型：
--
作者：
Xing, HR;Cordon-Cardo, C;Kolesnick, R
通过持续输注硫代磷酸反义寡核苷酸（ODNs）抑制ras-1（KSR 1）基因的激酶抑制因子，可阻止K-Ras依赖性人PANC-1胰腺癌和A549非小细胞肺癌裸鼠异种移植瘤的生长，影响已建立的PANC-1肿瘤的消退，并抑制A549肺转移，所有这些均无明显毒性。这些研究表明，KSR 1反义ODN作为Ras依赖性人类恶性肿瘤，特别是胰腺癌，缺乏有效的治愈性治疗的治疗。
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.