Tailor-made NK4-gene therapy for pancreatic cancer using nano devise.

我们开展了临床前研究，目的是通过腺病毒表达HGF的拮抗剂NK4，建立新的胰腺癌基因治疗方法。(2)研究了吉西他滨与Adeno-NK4联合治疗的疗效，证实了该疗法的协同作用。(3)经门脉注射Adeno-NK4对小鼠胰腺癌肝转移有明显的抑制作用。(4)我们利用表达NK4的细胞片开发了新型的药物传递系统，并表明新型DDS控制了小鼠胰腺癌的局部进展。(5)发现吉西他滨与纤维蛋白胶联合治疗有新的抑制作用，并继续进行临床试验。(6)建立了胰液标本快速诊断系统。(7.8)阐明了吉西他滨或放射增强腺病毒为基础的基因治疗的机制。(9)我们发现吉西他滨或其他抗癌药物也能加强以tert启动子为基础的CRAds治疗。

We performed preclinical studies to establish the novel gene therapy for pancreatic cancer using adenovirus expressing NK4, which is antagonist of HGF.We confirmed the safety of adno-NK4 using animal models. (2) We investigated the effect of combination therapy with gemcitabine and adeno-NK4 and demonstrated that synergistic effect of this therapy. (3)We revealed that trans-portal adeno-NK4 administration significantly inhibited the liver metastasis of pancreatic cancer in mouse models. (4) We developed novel drug delivery system using cell-sheet expressing NK4 and showed that the novel DDS controlled local progression of pancreatic cancer in mouse models. (5)We found the novel inhibitory effect of combination therapy with gemcitabine and fibrin glue and performed and continued the clinical trials using this therapy. (6) We developed rapid diagnostic system for pancreatic juice samples. (7.8) We clarified the mechanism of adenovirus-based gene therapy enhanced by gemcitabine or radiation.(9)We found that tert-promotor-medated CRAds therapy was also enhanced by gemcitabine or other anticancer agents.