Identification of new prognostic markers for esophageal cancer using molecular biologic techniques, and their clinical application for diagnosis and treatment.

利用分子生物学技术鉴定食管癌新的预后标志物及其在诊断和治疗中的临床应用。

基本信息

批准号：
09470264
负责人：
MAFUNE Ken-ichi
金额：
$ 8.58万
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：
1997
资助国家：
日本
起止时间：
1997 至 1999
项目状态：
已结题

项目摘要

Esophageal cancer usually behaves aggressively and carries a poor prognosis against intensive multimodality treatment Therefore, it is very important to identify novel prognostic markers for esophageal cancer. In this project, more than 20 cancer-related genes were selected using molecular biological techniques, such as differential screening, subtraction library, and differential display. Genetic changes, such as mutations, polymorphisms, and mRNA over expression, of these genes were examined in surgical specimens of esophageal cancer, and correlated with clinicopathologic factors. In this term of the project, we have published papers concerning telomerase activity, MAGE genes, omithine decarboxylase (ODC), integrin α6, Grb7, pyramiding nucleoside phosphorylase (PyNPase), and L-myc polymorphism. In addition, we have presented papers concerning insulin-like growth factor 2, p53, Rb, bcl-2, manganese super oxide dismutase, matrix metallopreteinase-7, point mutations and polymorphism of p53, and microsatellite instability in esophageal cancer at national aid international meetings. Of those genetic changes in esophageal cancer, mRNA expressions of ODC, integrin α6, Grb7, and PyNPase are candidates for prognostic factors. Among these candidates including other genes reported as prognostic factors (such as c-myc, EGF-receptor. hst-1/int-2, cycline D. and elongation factor-γ), Prognostic factors for esophageal cancer should be carefully selected. As clinical applications. ODC mRNA expression was also examined in endoscopic, biopsied specimens, and could be correlated with clinicopathologic factors. Furthermore. MAGE genes are now trying to apply immunotherapy.

食管癌通常表现出侵袭性，并且对强化多模式治疗的预后较差。因此，确定食管癌的新预后标志物非常重要。在该项目中，利用分子生物学技术（例如差异表达）选择了 20 多个癌症相关基因。在食管癌手术标本中检查这些基因的遗传变化，例如突变、多态性和 mRNA 过度表达，并与这些基因相关。在本期项目中，我们发表了有关端粒酶活性、MAGE基因、鸟氨酸脱羧酶（ODC）、整合素α6、Grb7、金字塔核苷磷酸化酶（PyNPase）和L-myc多态性的论文。发表有关胰岛素样生长因子 2、p53、Rb、bcl-2、锰超氧化物的论文在国家援助国际会议上，歧化酶、基质金属蛋白酶-7、p53的点突变和多态性以及食管癌的微卫星不稳定性在食管癌的这些遗传变化中，ODC、整合素α6、Grb7和PyNPase的mRNA表达是预测预后的候选指标。在这些候选因素中，包括其他被报告为预后因素的基因（例如 c-myc、EGF 受体）。 hst-1/int-2、cycline D. 和延伸因子-γ），作为临床应用，还应仔细选择食管癌的预后因素，并在内窥镜活检标本中检查 ODC mRNA 表达，并可能与临床病理学相关。此外，MAGE基因现在正在尝试应用免疫疗法。