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Pathology and molecular targeting of human pancreatic cancer

人类胰腺癌的病理学和分子靶向

基本信息

批准号：
17590291
负责人：
KIJIMA Hiroshi
金额：
$ 1.98万
依托单位：
Hirosaki University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590291/
关键词：
Cancer Metastasis Pancreas Gene regulation

项目摘要

Human pancreatic cancer is one of the most lethal malignancies because of rapid spread of the tumor, frequent incidence of metastasis and limitations of conventional therapy. Therefore, development of a new therapeutic strategy for pancreatic cancer such as molecular target therapy is one of the most pressing issues in current medicine. In this research projection, we designed ribozymes against K-ras gene and siRNA against claudin-1 gene, and examined growth suppression of human pancreatic cancer cells.RESULTS in 2005(1)Design of ribozymes. We designed anti-K-ras ribozyme against mutant K-ras gene transcripts, and generated a recombinant adenovirus to express the anti-K-ras ribozyme in the cells. However, we tried, but could not generate an adenovirus to express NF-kB gene transcripts.(2)Transfection of anti-K-ras ribozyme into the pancreatic cancer cells. Human pancreatic cancer cells were infected with adenovirus/anti-K-ras ribozyme. The ribozyme suppressed the target K-ras gene expression.RESULTS in 2006(1)Efficacy of the transfected ribozyme in the pancreatic cancer cells. The transfected adenovirus/anti-K-ras ribozyme suppressed the target gene expression, and affected increase of apoptosis and inhibition of angiogenesis in the pancreatic cancer tissue, resulting in growth of the pancreatic cancer cells.(2)Design of siRNA targeting claudin-1 gene. Claudin-1 plays a role in cell-to-cell attachment, and contributes cancer invasion. We designed anti-claudin-1 siRNA targeting claudin-1 gene transcripts. Anti-claudin-1 siRNA suppressed the target gene expression, as well as expression of matrix metalloproteinase-2 which is associated with cancer invasion in the stroma.Our results indicated that high-efficiency adenovirus-mediated delivery of anti-K-ras ribozyme and/or anti-claudin-1 siRNA could become a molecular target therapy against human pancreatic cancer in the future.

胰腺癌是人类最致命的恶性肿瘤之一，因为肿瘤的快速扩散，频繁发生转移和常规治疗的局限性。因此，开发胰腺癌的新的治疗策略，如分子靶向治疗是当前医学中最紧迫的问题之一。本研究设计了针对K-ras基因的核酶和针对claudin-1基因的siRNA，并研究了其对人胰腺癌细胞的生长抑制作用。我们针对突变型K-ras基因转录本设计了抗K-ras核酶，并构建了重组腺病毒，在细胞中表达抗K-ras核酶。然而，我们尝试了，但不能产生腺病毒表达NF-κ B基因转录本。（2）抗K-ras核酶转染胰腺癌细胞。用腺病毒/抗K-ras核酶感染人胰腺癌细胞。结果：2006年（1）转染核酶的胰腺癌细胞的疗效。转染腺病毒/抗K-ras核酶后，胰腺癌组织中靶基因的表达受到抑制，凋亡增加，血管生成受到抑制，从而促进胰腺癌细胞的生长。（2）针对claudin-1基因的siRNA设计。紧密连接蛋白-1在细胞与细胞的附着中起作用，并有助于癌症侵袭。我们设计了针对claudin-1基因转录物的抗claudin-1 siRNA。结果表明，抗claudin-1 siRNA能有效抑制靶基因的表达，同时也能抑制与胰腺癌间质侵袭相关的基质金属蛋白酶-2的表达，提示腺病毒介导的抗K-ras核酶和/或抗claudin-1 siRNA有可能成为胰腺癌的分子靶向治疗方法。

项目成果

期刊论文数量（15）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Mucin expression and proliferating cell index of esophageal Barrett's adenocarcinoma

食管Barrett腺癌粘蛋白表达及增殖细胞指数

DOI：
发表时间：
2005
期刊：
International Journal of Molecular Medicine 16
影响因子：
0
作者：
Yamamoto.S;Kijima H.;et al.
通讯作者：
et al.

57Arg in the bHLH transcription factor DEC2 is essential for the suppression of CLOCK/BMAL2-mediated transactivation

bHLH 转录因子 DEC2 中的 57Arg 对于抑制 CLOCK/BMAL2 介导的反式激活至关重要

DOI：
发表时间：
2006
期刊：
Int. J. Mol. Med 17
影响因子：
0
作者：
Kondo;J.;Sato;F.;Fujimoto;K.;Kusumi;T.;Imanaka;T.;Kawamoto;T.;Bhawal;U.K.;Noshiro;M.;Kato;Y.;Sato;T.;Kijima;H
通讯作者：
H

Gallbladder small cell carcinoma Xenograft established by serial transplantation in nude mice.

胆囊小细胞癌裸鼠连续移植建立的异种移植物。

DOI：
发表时间：
2006
期刊：
Anticancer Res. 26(1A)
影响因子：
0
作者：
Yoshiki A;Jan Mei-Ling;Mekada K;Yoshiki A;Ike F et al.;Nishime C.
通讯作者：
Nishime C.

Cell binding isoforms of vascular endothelial growth factor-A (VEGF189) contribute to blood flow-distant metastasis of pulmonary adenocarcinoma.

DOI：
10.3892/ijo.26.6.1517
发表时间：
2005-06
期刊：
International journal of oncology
影响因子：
5.2
作者：
M. Nishi;Y. Abe;Y. Tomii;H. Tsukamoto;H. Kijima;H. Yamazaki;Y. Ohnishi;M. Iwasaki;H. Inoue;Y. Ueyama;Masato Nakamura
通讯作者：
M. Nishi;Y. Abe;Y. Tomii;H. Tsukamoto;H. Kijima;H. Yamazaki;Y. Ohnishi;M. Iwasaki;H. Inoue;Y. Ueyama;Masato Nakamura

Interaction between Helicobacter pylori and immune response to CagA : CagA antibody may down-regulate bacterial colonization and tyrosine phosphorylation

幽门螺杆菌与 CagA 免疫反应之间的相互作用：CagA 抗体可能下调细菌定植和酪氨酸磷酸化