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.

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癌症生物学知识的增加而发展起来的一种新的分子治疗方法。更好地了解癌症生物学，特别是对肿瘤辐射抵抗机制的了解，导致了新的分子靶点的确定，可以用来提高放射治疗的治疗率。这些方法试图在几乎不影响正常组织反应的情况下，特别增加肿瘤的辐射反应。我们描述了目前联合放射治疗和分子靶向药物治疗口腔癌的方法。分子靶向药物(EGFR、COX-2、CDK、HSP90和血管生成抑制剂)可增强肿瘤的放射反应。由于肿瘤的异质性和多条放射耐药途径，肿瘤的反应各不相同。这些结果表明，相关分子靶标…的选择另一方面，为了确定与口腔癌放射治疗敏感性相关的基因，我们采用标准克隆形成实验，以7个口腔鳞癌细胞系为研究对象，通过基因芯片系统对放射敏感性进行评估。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。此外，我们还研究了口腔鳞癌患者术前放疗中成纤维细胞生长因子2、Friend白血病插入蛋白1和干扰素诱导基因6-16、G1P3等候选蛋白的表达水平与放疗疗效的关系。在对手术前放射治疗的反应和候选蛋白表达之间观察到显著的关联。这些数据应有助于确定辐射敏感性的预测标记物，并可能导致开发放射治疗的替代治疗方式。较少

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