权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Elucidation of the roles of Pim-1 induced under hypoxia in pancreatic cancer and its application to the cancer therapy

阐明缺氧诱导的Pim-1在胰腺癌中的作用及其在癌症治疗中的应用

基本信息

批准号：
16390202
负责人：
KOBAYASHI Masanobu
金额：
$ 9.28万
依托单位：
Hokkaido University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390202/
关键词：
Pim-1 hypoxia apoptosis resistance to anticancer drugs in vivo growth 膵がん癌遺伝子 PIM-1

项目摘要

In this study, we examined whether the inhibition of Pim-1 activity, is effective treatment pancreatic cancer, based on the findings that Pim-1 protein expression enhanced under hypoxic conditions. According to the previous reports demonstrating that the protein fused to polypeptides composed of eleven arginine can pass through the cytoplasmic membrane, we constructed an expression vector encoding 11 arginine-signal sequence of Thrombopoietin-dominant negative Pim-1 protein. PCI-43. cells, a pancreatic cancer cell line, were inoculated subcutaneously into the back of SCID mice. Then the mice were treated with the injection of the vectors into the femoral muscle. At 21 days after the treatment, the tumors in the mice treated with the injection of dominant negative PIM-1 expression vector disappeared, whereas the tumors in those treated with empty vector grew. These results suggest that the gene therapy using dominant negative Pim-1 expression vector may be effective for the cancer. However, the doses of expression vector to inject should be reduced for clinical trials. We sought small chemical compound library for the chemical compounds which could suppress the function of Pim-1. We found fourteen small chemical compounds which suppressed the phosphorylation activity of PIM-1 by more than 40 %. We are now planning to examine the in vivo anti-tumor effects of those compounds.

在本研究中，我们基于低氧条件下Pim-1蛋白表达增强的发现，探讨了抑制Pim-1活性是否有效治疗胰腺癌。根据以往报道的11个精氨酸组成的多肽可以穿透细胞膜的报道，我们构建了编码11个精氨酸信号序列的Pim-1蛋白的表达载体。PCI-43。将胰腺癌细胞株接种于SCID小鼠背部皮下。然后，将载体注射到小鼠的股部肌肉中。治疗21d后，注射显性负性PIM-1表达载体的小鼠肿瘤消失，而注射空载体的小鼠肿瘤生长。这些结果提示，使用显性负性Pim-1表达载体进行基因治疗对肿瘤可能是有效的。然而，临床试验中应减少表达载体的注射剂量。我们为抑制Pim-1功能的化合物寻找小的化合物文库。我们发现有14个小分子化合物对PIM-1的磷酸化活性有40%以上的抑制作用。我们现在正计划检查这些化合物的体内抗肿瘤作用。

项目成果

期刊论文数量（21）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Acetylcholine from vagal stimulation protects cardiomyocytes against ischemia and hypoxia involving additive non-hypoxic induction of HIF-1α

DOI：
10.1016/j.febslet.2005.02.065
发表时间：
2005-04-11
期刊：
FEBS LETTERS
影响因子：
3.5
作者：
Kakinuma, Y;Ando, M;Sato, T
通讯作者：
Sato, T

Cytolytic activity and regulatory functions of inhibitory NK cell receptor-expressing T cells expanded from peripheral blood mononuclear cells.

表达抑制性 NK 细胞受体的 T 细胞从外周血单核细胞扩增而来的溶细胞活性和调节功能。

DOI：
发表时间：
2004
期刊：
Blood 104
影响因子：
0
作者：
Wang;JQ.;Kon;J.;Mogi;C.;Tobo;M.;Damirin;A.;Sato;K.;Komachi;M.;Malchinkhuu;E.;Murata;N.;Kimura;T.;Kuwabara;A.;Wakamatsu;K.;Koizumi;T.;Uede;T.;Tsujimoto;G.;Kurose;H.;Sato;T.;Harada;A.;Misawa;N.;Tomura;H.;Okajima;F.;Takaku H;Takaku H;Matsuda N;Koike T;Kondo K;Tanaka J
通讯作者：
Tanaka J

Hypoxia suppresses the production of matrix metalloprote-inases and the migration of human monocyte-derived dentritic cells.

缺氧会抑制基质金属蛋白酶的产生和人单核细胞衍生的树突细胞的迁移。

DOI：
发表时间：
2005
期刊：
Eur J Immunol 35
影响因子：
0
作者：
成瀬達;石黒洋;成瀬達;成瀬達;Okada F;Okada F;Miseki T;Okada F et al.;Kakinuma Y;Suzuki A;Zhao W
通讯作者：
Zhao W

Hypoxia suppresses the production of matrix metalloproteinases and the migration of humanmonocyte‐derived dendritic cells

DOI：
10.1002/eji.200526262
发表时间：
2005-12
期刊：
European Journal of Immunology
影响因子：
5.4
作者：
Wenli Zhao;S. Darmanin;Q. Fu;Jian Chen;Hongyan Cui;Jingxin Wang;F. Okada;J. Hamada;Y. Hattori;T. Kondo;J. Hamuro;M. Asaka;Masanobu Kobayashi
通讯作者：
Wenli Zhao;S. Darmanin;Q. Fu;Jian Chen;Hongyan Cui;Jingxin Wang;F. Okada;J. Hamada;Y. Hattori;T. Kondo;J. Hamuro;M. Asaka;Masanobu Kobayashi

Prevention of inflammation-mediated acquisition of metastatic properties of benign mouse fibrosarcoma cells by administration of an orally available SOD.

通过口服 SOD 来预防炎症介导的良性小鼠纤维肉瘤细胞的转移特性。