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Characterization of novel therapeutic target oncogenes using gene-targeted somatic cells

使用基因靶向体细胞表征新的治疗靶标癌基因

基本信息

批准号：
16390099
负责人：
DAIGO Yataro
金额：
$ 7.1万
依托单位：
The University of Tokyo
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 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390099/
关键词：
Cancer related genes Homologous recombination 体細胞遺伝子相同組み換え

项目摘要

Over the last decade, a number of molecular targets and biomarkers for cancer therapy have been reported. However, suppression of some of the target molecules can provide survival benefits to a small subset of the patients, and only a limited number of practical biomarkers are presently available for selection of treatment modalities. In order to identify molecules involved in pulmonary and esophageal carcinogenesis and those which could be useful as therapeutic biomarkers for lung and esophageal cancer, we have established an effective screening system. The strategy was as follows ; i) To identify up-regulated genes in lung cancers by genome-wide screening using the cDNA microarray representing 32,256 genes and pure populations of tumor cells taken from 120 lung and esophageal cancer tissues by laser microdissection, ii) To verify the candidate genes for their very low level of expression in normal tissues by cDNA microarray and northern-blot analyses, iii) To validate the clinicopathological significance of its over-expression by means of tissue microarray containing hundreds of archived lung-cancer samples, iv) To verify whether the target gene is essential for the cell growth or motility of cancer cells by RNAi and cell growth/invasion assays, v) To evaluate its function and relevant molecular pathways by use of the gene-targeting technology for somatic cells. Through this systematic approach, we identified a set of molecules that appear to fall into the category of cancer-testis antigens and whose up-regulation is a frequent and important feature of the malignant nature of cancer. We provided evidence to indicate that the molecules identified can be regarded as potential targets for the development of highly sensitive and specific biomarkers as well as being useful in the development of small-molecular compounds, antibodies, and cancer vaccines that could have a more specific and efficient anti-cancer effect with minimal risk of adverse effects.

在过去的十年中，已经报道了许多用于癌症治疗的分子靶标和生物标志物。然而，抑制一些靶分子可以为一小部分患者提供生存益处，目前只有有限数量的实用生物标志物可用于选择治疗方式。为了鉴定参与肺和食管癌发生的分子以及那些可能用作肺和食管癌治疗生物标志物的分子，我们建立了一个有效的筛选系统。战略如下：i）使用代表32，256个基因的cDNA微阵列和通过激光显微切割从120个肺癌和食管癌组织中获取的肿瘤细胞的纯群体，通过全基因组筛选来鉴定肺癌中的上调基因，ii）通过cDNA微阵列和Northern印迹分析来验证候选基因在正常组织中的非常低的表达水平，iii）通过包含数百个存档的肺癌样品的组织芯片验证其过表达的临床病理学意义; iv）通过RNAi和细胞生长/侵袭测定验证靶基因是否是癌细胞的细胞生长或运动所必需的; v）通过使用体细胞基因靶向技术评估其功能和相关分子通路。通过这种系统的方法，我们确定了一组分子，似乎属于癌症睾丸抗原的类别，其上调是癌症恶性性质的一个常见和重要的特征。我们提供的证据表明，所鉴定的分子可被视为开发高度敏感和特异性生物标志物的潜在靶点，并可用于开发小分子化合物、抗体和癌症疫苗，这些化合物、抗体和癌症疫苗可具有更特异和有效的抗癌作用，且不良反应的风险最小。

项目成果

期刊论文数量（12）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Gene expression profiles of small-cell lung cancers: molecular signatures of lung cancer.

DOI：
10.3892/ijo.29.3.567
发表时间：
2006-09
期刊：
International journal of oncology
影响因子：
5.2
作者：
M. Taniwaki;Y. Daigo;N. Ishikawa;A. Takano;T. Tsunoda;W. Yasui;K. Inai;N. Kohno;Yusuke Nakamura
通讯作者：
M. Taniwaki;Y. Daigo;N. Ishikawa;A. Takano;T. Tsunoda;W. Yasui;K. Inai;N. Kohno;Yusuke Nakamura

ADAM8 as a novel serological and histochemical marker for lung cancer

DOI：
10.1158/1078-0432.ccr-04-1436
发表时间：
2004-12-15
期刊：
CLINICAL CANCER RESEARCH
影响因子：
11.5
作者：
Ishikawa, N;Daigo, Y;Nakamura, Y
通讯作者：
Nakamura, Y

分子呼吸器病

分子呼吸系统疾病

DOI：
发表时间：
2015
期刊：
影响因子：
0
作者：
Kamata H;Yamamoto K;Wasserman GA;Zabinski MC;Quinton LJ;Jones MR;Mizgerd JP.;山本和子
通讯作者：
山本和子

Prediction of response to neoadjuvant chemotherapy for osteosarcoma by gene-expression profiles.

DOI：
10.3892/ijo.24.3.647
发表时间：
2004-03
期刊：
International journal of oncology
影响因子：
5.2
作者：
K. Ochi;Y. Daigo;T. Katagiri;S. Nagayama;T. Tsunoda;A. Myoui;N. Naka;N. Araki;I. Kudawara
通讯作者：
K. Ochi;Y. Daigo;T. Katagiri;S. Nagayama;T. Tsunoda;A. Myoui;N. Naka;N. Araki;I. Kudawara

The neuromedin U-growth hormone secretagogue receptor 1b/neurotensin receptor 1 oncogenic signaling pathway as a therapeutic target for lung cancer