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

INTRACELLULAR FREE CA2+ AND ANTICANCER DRUG ACTION

细胞内游离 CA2 和抗癌药物作用

基本信息

批准号：
3183371
负责人：
GARTH POWIS
金额：
$ 19.33万
依托单位：
UNIVERSITY OF ARIZONA
依托单位国家：
美国
项目类别：
财政年份：
1986
资助国家：
美国
起止时间：
1986-04-01 至 1993-11-30
项目状态：
已结题

项目摘要

A fundamental difference between normal cells and cancer cells is the expression of oncogenes in cancer cells and the independence of cancer cells from many growth factors for proliferation. Recent work suggests that the function of oncogenes is to code for components of intracellular signal transduction pathways for growth factors, thus, relieving the cancer cell of the normal requirements for growth factors. Eukaryotic cells maintain very low levels of intracellular free Ca2+ ([Ca2+]i) which are over 10,000-fold lower than extracellular Ca2+. The low levels and the exquisite control exerted by the cell over [Ca2+]i allow small changes in [Ca2+]i to be used as a highly responsive intracellular messenger for carrying signals from growth factors acting on receptors at the cell surface to the nucleus. The close relationship between growth factor and oncogene action indicates that changes in [Ca2+]i are also important in mediating the effects of oncogenes. The hypothesis upon which our studies are based is that by developing agents that effect the way [Ca2+]i and related second messengers mediate the effects of growth factors and oncogenes it should be possible to exploit basic biological differences between normal cells and cancer cells for the selective treatment of cancer. To do this effectively we need a better understanding of the role of [Ca2+]i and related second messengers in the control of normal and cancer cell growth factors and oncogenes. We also need to identify compounds that selectively block [Ca2+]i signalling pathways in tumor cells. Our studies are, therefore, focused on understanding the mechanisms of growth factor and oncogene and signal transduction involving [Ca2+]i and related second messengers, and the relationship to cell proliferation. We will employ a number of approaches for measuring [Ca2+]i, Ca2+ fluxes, as well as other intracellular second messengers in defined, growth factor- dependent cell systems. We have identified five novel classes of agents that block [Ca2+]i signalling that may be prototypes for new classes of cell growth inhibitors. The ultimate objective of our studies is to find new ways of treating cancer through target directed drug discovery.

正常细胞和癌细胞的根本区别是

项目成果

期刊论文数量（48）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Signalling pathways as targets for anticancer drug development.

信号通路作为抗癌药物开发的靶点。

DOI：
10.1016/0163-7258(94)90005-1
发表时间：
1994
期刊：
Pharmacology & therapeutics
影响因子：
13.5
作者：
Powis,G
通讯作者：
Powis,G

Inhibiting intracellular signalling as a strategy for cancer chemoprevention.

抑制细胞内信号传导作为癌症化学预防的策略。

DOI：
10.1016/0959-8049(94)90473-1
发表时间：
1994
期刊：
European journal of cancer (Oxford, England : 1990)
影响因子：
0
作者：
Powis,G;Alberts,DS
通讯作者：
Alberts,DS

A multisample assay for inhibitors of phosphatidylinositol phospholipase C: identification of naturally occurring peptide inhibitors with antiproliferative activity.

DOI：
发表时间：
1994-08
期刊：
Anti-cancer drug design
影响因子：
0
作者：
Hill;R. Bonjouklian;Garth Powis;Abraham Rt;Ashendel Cl;Zalkow Lh
通讯作者：
Hill;R. Bonjouklian;Garth Powis;Abraham Rt;Ashendel Cl;Zalkow Lh

The thioredoxin/thioredoxin reductase redox system and control of cell growth.

DOI：
发表时间：
1994
期刊：
Oncology research
影响因子：
3.1
作者：
Garth Powis;J. Oblong;P. Gasdaska;M. Berggren;Simon R. Hill;D. Kirkpatrick
通讯作者：
Garth Powis;J. Oblong;P. Gasdaska;M. Berggren;Simon R. Hill;D. Kirkpatrick

Inhibition of growth factor-dependent inositol phosphate Ca2+ signaling by antitumor ether lipid analogues.

抗肿瘤醚脂质类似物抑制生长因子依赖性磷酸肌醇 Ca2 信号传导。