Effects of oxidant balance on colon and breast cancer

描述(由申请人提供)： 主要的主题思想是局部和全身的氧化剂平衡是关键 结肠起始、进展和转移转化的决定因素 和乳腺癌。调节局部和全身氧化剂平衡的可能性 将对饮食进行调查，以确定遗传和功能 癌症进展的后果。选择性肿瘤模型 适当界定原位转化、扩散、侵袭和 转移将与遗传和功能分析结合使用，以 明确定义癌症进展中的这些事件。该计划的一部分将是 旨在消除饮食诱导的癌症基因表达的变化， 与癌症进展途径中的特定步骤相对应。特定的 基因调控事件可被描述为对 肿瘤的发生、侵袭或转移。可复制的基因表达变化 在肿瘤细胞或宿主中观察到，并与PRO-OR相关 抗氧化状态，将被进一步开发为独立的生物标志物 依赖氧化剂平衡的致癌事件。氧化剂状态的生物标志物 将确定在肿瘤部位建立基线氧化剂平衡 在整个时间内的启动和发展以及在循环中 每种肿瘤进展模型的病程。饮食干预将是 被用作促进和抗氧化治疗，以确定其贡献 或改变观察到的氧化剂平衡水平和 相应的肿瘤进展事件。总体方案方法将 必须定义特定的积极事件和消极事件 饮食成分，尤指那些影响局部或整体氧化剂的成分 平衡，将对选定的致癌事件产生影响。氧化剂的应用 这些模型中定义的生物标志物筛选方法将应用于 人体肿瘤(即局部氧化剂平衡)以及循环血清水平 将与肿瘤状态和诊断相关。因此，一个长期目标是 这项合作将定义人类的基线氧化剂状态 患者取决于他们的肿瘤类型、目前的治疗方法、饮食和生活方式 各种因素。此外，在整个过程中持续监测氧化剂平衡 化疗和放射治疗、新的治疗方法和改变 在饮食和生活方式中可以采用的是附加性的长期目标 程序。

DESCRIPTION (provided by applicant): The primary thematic idea that the local and systemic oxidant balance is a key determinant for the initiation, progression and metastatic conversion of colon and breast cancers. Potential to modulate local and systemic oxidant balance with diet will be investigated to determine the genetic and functional consequences for cancer progression. Selective cancer models which appropriately define in situ transformation, proliferation, invasion and metastasis will be used in conjunction with genetic and functional analyses to clearly define these events in cancer progression. Part of the program will be directed towards defming diet-induced changes in cancer gene expression that correspond to particular steps in the cancer progression pathway. Specific gene regulating events may be delineated as positive or negative effecters of tumorigenesis, invasion or metastasis. Reproducible gene expression changes observed in tumor cells or the host and can be correlated to pro- or anti-oxidant status, will then be further developed as independent biomarkers of oxidant balance-dependent tumorigenic events. Biomarkers of oxidant status will be determined to establish baseline oxidant balance at the site of tumor initiation and progression as well as in the circulation over the entire time course of each tumor progression model. Dietary interventions will be employed as pro- and anti-oxidant treatments to determine their contribution or alteration to both the level of oxidant balance observed and the corresponding tumor progression events. The overall programatic approach will necessarily define the particular positive and negative events for which dietary constituents, especially those that affect local or overall oxidant balance, will have on select tumorigenic events. Application of oxidant biomarker screening methods defined in these models will then be applied to human tumors (i.e. local oxidant balance), as well as circulating serum levels will be correlated to tumor status and diagnosis. Thus, a long-term goal of this collaboration will be to define baseline oxidant status for human patients depending on their tumor type, current treatment, diet and lifestyle factors. In addition, continued oxidant balance monitoring through the course of treatments, such as chemo and radiotherapies, new therapeutics and changes in diet in lifestyle which may be employed are additive long term goals of the program.