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PRIMING OF PANCREATIC TUMORS CELLS AND CANCER STEM CELLS TO TRAIL-INDUCED APOPTOSIS

机译:胰腺肿瘤细胞和癌干细胞向肿瘤诱导的细胞凋亡的启动

摘要

The present invention relates particularly to use of JNK inhibition together with administration of TRAIL to selectively suppress cancer stem cells. The present inventors undertook to identify selective molecular pathways that would be highly effective in inhibiting cancer growth, specifically that of cancer stem cells. In one embodiment provided herein a method of treating pancreatic cancer in a patient is provided that includes administration of a low-dose of a c-Jun N-terminal kinase (JNK) inhibitor in combination with a low-dose of a TNF-related apoptosis-inducing ligand (TRAIL"). In certain embodiments the low-dose of the JNK inhibitor is a dose that corresponds to an in vitro dose that will reduce cell viability in a pancreatic cell line by 20% or less. In certain specifically exemplified embodiments, the low-dose of TRAIL is a dose that corresponds to a dose of 1 mg/kg or less.
机译:本发明尤其涉及JNK抑制与TRAIL的施用一起用于选择性抑制癌症干细胞的用途。本发明人致力于鉴定在抑制癌症生长,特别是癌症干细胞的生长方面非常有效的选择性分子途径。在本文提供的一个实施方案中,提供了一种治疗患者的胰腺癌的方法,该方法包括给予低剂量的c-Jun N末端激酶(JNK)抑制剂与低剂量的TNF相关的细胞凋亡组合-诱导性配体(TRAIL-)。在某些实施方案中,低剂量的JNK抑制剂是对应于将使胰腺细胞系中的细胞生存力降低20%或更少的体外剂量的剂量。 ,TRAIL的低剂量是相当于1 mg / kg或更少的剂量。

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