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Analysis of abnormality for check point mechanism regulation by DNA damage with radiation therapy for Oral cancer treatment and molecular target therapy against this mechanism.

口腔癌放射治疗及针对该机制的分子靶向治疗对DNA损伤调节检查点机制的异常分析。

基本信息

批准号：
16390592
负责人：
SHINTANI S.
金额：
$ 8.77万
依托单位：
Showa University (2006)Ehime University (2004-2005)
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

项目摘要

Radiation therapy continues to remain a major treatment modality for oral cancers. Molecular targeting therapy developed as new molecular approaches derived from the recent increase in the knowledge of cancer biology. A better understanding of cancer biology and in particular of tumor radiation resistance mechanisms led to the identification of new molecular targets that could used to increase the therapeutic ratio of radiation therapy. These approaches attempt to increase specifically tumor radiation response with little impact on normal tissue response. We described the current approach of combined radiation with molecular targeting agents relevant for the treatment of oral cancer. Molecular targeting agents (Inhibitors of EGFR, COX-2, CDK, HSP90 and angiogenesis) enhanced the radio-response of tumors. Because of tumor heterogeneity and the multiple radio-resistance pathways, the responses of tumors were varied. These results suggested that the selection of relevant molecular targeti … More ng agents based on molecular biological information will be necessary for improvement of radiation enhancement.On the other hand, to determine genes that correlating with radiation sensitivity of oral cancer treatment, we evaluated radiation sensitivity assessed by a standard colony formation assay with a gene microarray system with 7 OSCC cell lines. We found significant associations between dozens of genes expression levels and radiation resistance of OSCC cell lines. We also evaluated the relationship between expression levels of some candidate proteins, i.e. fibroblast growth factor (FGF) 2, friend leukemia inserton (Fli)-1 and an interferon inducible gene 6-16, G1P3, and radiation therapeutic effectiveness in OSCC patients of treated with preoperative radiation therapy. The significant association between the response to preoperative radiation therapy and candidate proteins expressions were observed. These data should contribute useful information for identifying predictive markers for radiation sensitivity, and may lead to the development of alternative treatment modalities for radiation therapy. Less

放射治疗仍然是口腔癌的主要治疗方式。分子靶向治疗是近年来随着肿瘤生物学研究的深入而发展起来的一种新的分子治疗方法。对癌症生物学，特别是肿瘤辐射抗性机制的更好理解导致了新的分子靶点的鉴定，这些靶点可用于提高放射治疗的治疗率。这些方法试图特异性地增加肿瘤辐射反应，而对正常组织反应的影响很小。我们描述了目前的方法结合放射治疗与分子靶向药物相关的口腔癌的治疗。分子靶向药物（EGFR、考克斯-2、CDK、HSP 90和血管生成抑制剂）增强了肿瘤的放射反应。由于肿瘤的异质性和多种放射抗性途径，肿瘤的反应是不同的。这些结果表明，选择相关的分子靶点， ...更多信息另一方面，为了确定与口腔癌治疗辐射敏感性相关的基因，我们采用标准集落形成试验，利用基因芯片系统对7种口腔鳞癌细胞系进行了辐射敏感性评估。我们发现几十个基因的表达水平与口腔鳞癌细胞系的辐射抗性之间存在显著的相关性。我们还评估了一些候选蛋白，即成纤维细胞生长因子（FGF）2，朋友白血病插入子（Fli）-1和G1P3，干扰素诱导基因6 - 16的表达水平与术前放射治疗的OSCC患者的放射治疗效果之间的关系。观察到对术前放射治疗的反应与候选蛋白表达之间的显著相关性。这些数据应有助于识别辐射敏感性的预测标志物的有用信息，并可能导致放射治疗的替代治疗方式的发展。少