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Alterations in oncogenes and tumor suppressor genes on human lung cancer as a treament guideline

人类肺癌癌基因和抑癌基因的改变作为治疗指南

基本信息

批准号：
04454351
负责人：
MITSUDOMI Tetsuya
金额：
$ 2.3万
依托单位：
KYUSHU UNIVERSITY (1994)University of Occupational and Environmental Health, Japan (1992-1993)
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1994
项目状态：
已结题

项目摘要

The objective of the present study is to investigate various genetic lesions in human lung cancer and to correlate the findings with clinicopathological features including patient prognosis.First, we examined 120 cases of lung cancer operated on at the Fukuoka University and the University of Occupational and Environmental Health, Japan (UOEH) for p53 mutations. We showed that p53 mutations were a poor prognostic factor especially in advanced cases. However, this cohort was from two institutions and was not fully consecutive. The following analysis was performed using 129 patients out of 140 consecutive patients who were treated at the UOEH.We examined this cohort for p53 abnormality at a DNA and protein level using immunohistochemistry and SSCP analysis, respectively. In this cohort, p53 mutations were a poor prognostic factor in adenocarcinoma, but there was no significant impact on survival in squamous cell carcinoma.We then examined loss of heterozygosity at the 3p.5q, 9p locus usi … More ng a microsatellite polymorphism in collaboration with Dr.Adi Gazdar at the University of Texas. LOHs were found in 51,31 and 23%, respectively. Patients with 3p LOH had a poor prognosis in early stage group. However, the other lesions seemed not to be correlated with patient prognosis. Loss of expression of retinoblastoma gene was examined using immunohistochemistry in collaboration with Dr.William Benedict at the Baylor College of Medicine. This abnormality was found in 22% of cases, butthere was no relationship with patient prognosis.Multivariate analysis for overall survival including above genetic lesions revealed that completeness of the resection was the only determinant for a poor prognosis. However, for a disease free interval in stage I patients, the multivariate analysis indicated that 3p LOH was the only significant predictor for an early disease relapse.In conclusion, p53 and 3p may be useful markers for clinical oncology of lung cancer. However, there were no genetic prognostic indicator superior to the marker such as a disease stage which are being used routinely. Less

本研究的目的是调查各种遗传病变在人类肺癌和相关的临床病理特征，包括患者预后的研究结果，首先，我们研究了120例肺癌手术在福冈大学和大学的职业和环境卫生，日本（UOEH）的p53突变。我们发现p53突变是一个预后不良的因素，尤其是在晚期病例中。然而，该队列来自两个机构，并且不是完全连续的。我们对140例连续接受UOEH治疗的患者中的129例进行了以下分析，分别采用免疫组化和SSCP分析在DNA和蛋白水平上检测了该队列的p53异常。在这个队列中，p53突变是腺癌预后不良的因素，但对鳞状细胞癌的生存率没有显著影响。 ...更多信息 ng微卫星多态性与德克萨斯大学的阿迪·加兹达尔博士合作。LOH检出率分别为51%、31%和23%。3 p洛缺失早期组预后差。然而，其他病变似乎与患者预后无关。与贝勒医学院的威廉·本尼迪克特博士合作，使用免疫组织化学检查了视网膜母细胞瘤基因表达的缺失。多因素分析表明，包括上述基因病变在内的总生存率的多因素分析表明，切除完整性是预后不良的唯一决定因素。多因素分析显示，对于I期患者的无病期，3p洛是唯一有意义的早期复发预测因子，p53和3p可能是肺癌临床肿瘤学的有用标志物。然而，没有优于常规使用的标记物如疾病阶段的遗传预后指标上级。少