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

使用纳米装置针对胰腺癌量身定制 NK4 基因疗法。

• 批准号: 16209040
• 负责人: TANAKA Masao
• 金额: $ 31.95万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16209040/
• 关键词: Pancreatic cancer; NK4; HGF; drug delivery system; adenovirus; gene therapy; 遺伝子治療

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.

我们进行了腺病毒介导的肝细胞生长因子（HGF）拮抗剂NK 4基因治疗胰腺癌的临床前研究，并通过动物模型证实了Adno-NK 4的安全性。(2)我们研究了吉西他滨和腺-NK 4联合治疗的效果，并证明了这种治疗的协同作用。(3)We显示经门静脉腺-NK 4施用显著抑制小鼠模型中胰腺癌的肝转移。(4)我们利用表达NK 4的细胞片层开发了新型药物递送系统，并显示新型DDS在小鼠模型中控制胰腺癌的局部进展。(5)We发现了吉西他滨和纤维蛋白胶联合治疗的新的抑制作用，并使用该疗法进行并继续进行临床试验。(6)建立了胰液样品快速诊断系统。(7.8)我们阐明了吉西他滨或放射增强腺病毒基因治疗的机制。(9)We发现叔启动子介导的CRAds疗法也被吉西他滨或其他抗癌剂增强。

项目成果

Peritumoral injection of adenovirus vector expressing NK4 combined with gemcitabine treatment suppresses growth and metastasis of human pancreatic cancer cells implanted orthotopically in nude mice and prolongs survival

• DOI: 10.1038/sj.cgt.7700921
• 发表时间: 2006-05
• 期刊: Cancer Gene Therapy
• 影响因子: 6.4
• 作者: Y. Ogura;K. Mizumoto;E. Nagai;M. Murakami;N. Inadome;M. Saimura;K. Matsumoto;T. Nakamura;M. Maemondo;T. Nukiwa;M. Tanaka

New infusion device for trans-tissue, sustained local dehvery of anticancer agent to surgically resected tissue: Potential use for suppression of local recurrence of pancreatic cancer

用于跨组织、持续局部输送抗癌剂至手术切除组织的新型输注装置：抑制胰腺癌局部复发的潜在用途

• 发表时间: 2004
• 期刊: J Biomed Master Res B Appl Biomater 73
• 作者: Manabe T;et. al.
• 通讯作者: et. al.

Suppression of metastasis of human pancreatic cancer to the liver by transportal injection of recombinant adenoviral NK4 in nude mice.

裸鼠体内转运注射重组腺病毒NK4抑制人胰腺癌肝转移。

• 发表时间: 2005
• 期刊: Int J Cancer. 117・1
• 作者: 鈴木隆史;山本雅之;Ogura Y.et al.;Murakami M.et al.
• 通讯作者: Murakami M.et al.

S100P is an early developmental marker of pancreatic carcinogenesis

• DOI: 10.1158/1078-0432.ccr-06-0298
• 发表时间: 2006-09-15
• 期刊: CLINICAL CANCER RESEARCH
• 影响因子: 11.5
• 作者: Ohuchida, Kenoki;Mizumoto, Kazuhiro;Tanaka, Masao
• 通讯作者: Tanaka, Masao

Strategy for prevention of local recuttence of pancreatic cancer after pancreatectomy : antitumor effect of gemcitabine mixed with fibrin glue in an orthotopic nude mouse model

预防胰腺癌术后局部复发的策略：吉西他滨与纤维蛋白胶混合对原位裸鼠模型的抗肿瘤作用

• 发表时间: 2006
• 期刊: Surgery 140・1
• 作者: Kawaguchi AT;Tsukada H;et al.;Ogura Y et al.
• 通讯作者: Ogura Y et al.