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Clinical approach of cancer of the esophagus specific treatment based on an individualization of a gene expression pattern

基于基因表达模式个体化的食管癌特异性治疗的临床方法

基本信息

批准号：
16390387
负责人：
KONDO Satoshi
金额：
$ 8.06万
依托单位：
HOKKAIDO UNIVESITY
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-16390387/
关键词：
esophageal cancer gene diagnosis E2F-1 DARPP-32 CyclinD1 PEDF gene therapy 予後腫瘍特異的抗原マイクロアレイ

项目摘要

We investigated the immunoreactivity of E2F-1,DARPP-32,CyclinD1, and PEDF in 122 patients with esophageal squamous cell cancer. (ESCC) Subsequently, we analyzed the correlation between the gene expression and clinicopathological features. Overexpression of E2F-1 or CyclinD1 correlatesd with tumor progression and s worse prognosis after surgery in ESCC. Moreover, we performed a mufti-institutional analysis of E2F-1 and cyclinD1 expression in patients with ESCC. E2F-1/cyclinD1(-/-) tumors correlated with reduced tumor progression. DARPP-32 expression was hardly seen in normal esophageal mucous and dysplasia, but it arised after a phase of dysplasia in ESCC. However, patients with DARPP-32 positive tumor showed a favorable prognosis. Expression of t-DARPP, which is one of DARPP isoforms, was not seen in ESCC. PEDF expression was seen in normal esophageal mucous and its expression in ESCC inversely correlated with the malignant features. Downregulation of PEDF correlated with lymph nodal metastasis. Then, genetic diagnoses of E2F-1,DARPP-32,CyclinD1, and PEDF expressions would be useful to assess the malignancy of ESCC. Moreover, since secreted PEDF from cells suppresses the growth and the migration of surrounding vascular endothelial cells, PEDF gene therapy may provide a new approach for treatment of cancer.

我们检测了122例食管鳞癌组织中E2F-1、DARPP-32、细胞周期蛋白D1和PEDF的表达。(ESCC)随后，我们分析基因表达与临床病理特征的相关性。食管癌组织中E2F-1和Cyclin D1的过度表达与肿瘤进展和S预后不良有关。此外，我们还对E2F-1和细胞周期蛋白D1在ESCC患者中的表达进行了多机构分析。E2F-1/Cyclin D1(-/-)肿瘤与肿瘤进展减慢相关。DARPP-32在正常食道粘膜和异型增生中几乎未见表达，但在食管鳞癌中出现在异型增生后一段时间。然而，DARPP-32阳性的肿瘤患者预后良好。食管鳞癌中未见DARPP亚型t-DARPP的表达。PEDF在正常食道粘膜中的表达与食管鳞癌的恶性程度呈负相关。PEDF表达下调与淋巴结转移相关。因此，对E2F-1、DARPP-32、细胞周期蛋白D1和PEDF的基因诊断将有助于评估ESCC的恶性程度。此外，由于细胞分泌的PEDF抑制周围血管内皮细胞的生长和迁移，PEDF基因治疗可能为癌症的治疗提供一种新的途径。