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

我们进行了临床前研究，利用表达HGF拮抗剂NK4的腺病毒建立新的胰腺癌基因治疗方法。我们用动物模型证实了adno-NK4的安全性。(2)我们研究了吉西他滨和腺- nk4联合治疗的效果，并证明了该治疗的协同效应。(3)我们发现，在小鼠模型中，经门静脉腺- nk4给药可显著抑制胰腺癌肝转移。(4)我们利用表达NK4的细胞片开发了一种新的给药系统，并在小鼠模型中发现这种新型DDS可以控制胰腺癌的局部进展。(5)我们发现吉西他滨与纤维蛋白胶联合治疗的新抑制作用，并开展并继续使用该疗法的临床试验。(6)研制了胰液样品快速诊断系统。（7.8）阐明了吉西他滨或放疗增强腺病毒基因治疗的机制。(9)我们发现吉西他滨或其他抗癌药物也能增强三启动子介导的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.