HUMAN TUMOR HYPOXIA

人类肿瘤缺氧

• 批准号: 2012064
• 负责人: JAMES ARTHUR RALEIGH
• 金额: $ 14.45万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-19 至 1999-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2012064
• 关键词: biomarker; cell proliferation; cervix neoplasms; clinical research; female; gene expression; histopathology; human subject; hypoxia; method development; neoplastic growth; oxygen microelectrode; stress proteins

DESCRIPTION: (Adapted from the applicant's abstract): Normal and tumor tissue hypoxia is associated with heart attack, stroke and cancer and may be a key factor in diabetes and alcohol-induced liver disease. Cancer specialists have long been interested in tissue hypoxia because hypoxic cells are radioresistant due to altered free radical chemistry and chemoresistant due low drug concentration in hypoxic cells that are at or near the limit of drug diffusion. On a more positive note, hypoxic tumor cells might be targets for improved therapy through bioreductive strategies. Finally, hypoxia (or hypoxia/reperfusion) is now recognized as a stress leading to gene expression in normal and tumor tissue that can be beneficial or harmful depending on circumstances. With the heightened interest in hypoxia in both normal and tumor tissue has come an urgent need for versatile and reliable methods for measuring tissue oxygenation. Many techniques have been proposed including hypoxia markers and oxygen microelectrodes. The primary goal of the present proposal is to make the first direct comparison between these two techniques in human tumors in collaboration with investigators at Aarhus University Hospital in Aarhus, Denmark. Such a comparison was called for in a 1992 NIH Oxygen Workshop. Our hypoxia marker will be injected into patients and 8 hours later oxygen electrode measurements made in the tumor followed by tissue biopsy for hypoxia marker binding by immunohistochemical analysis. The hypoxia marker approach lends itself to comparison with other features of tumor physiology related to therapeutic response. One such comparison to be carried out on the same biopsy sample will be with tumor cell proliferation (Ki-67). We believe that the hypoxia marker technique will be useful in radiation and chemotherapy treatment planning; for studies of tissue oxygenation in models of normal tissue pathologies; and, for relating hypoxia to the expression of stress proteins on a microregional basis.

描述：（改编自申请人的摘要）：正常和肿瘤 组织缺氧与心脏病、中风和癌症有关，并且可能是 糖尿病和酒精性肝病的关键因素。 癌症 专家们长期以来对组织缺氧感兴趣，因为缺氧 由于自由基化学的改变，细胞具有抗辐射性 由于处于或处于缺氧状态的细胞中药物浓度低而产生化学抗性 接近药物扩散极限。 从更积极的角度来看，缺氧肿瘤 细胞可能是通过生物还原策略改进治疗的目标。 最后，缺氧（或缺氧/再灌注）现在被认为是一种压力 导致正常和肿瘤组织中的基因表达，这可能是有益的 或有害，视具体情况而定。 随着人们对正常组织和肿瘤组织缺氧的兴趣日益浓厚 迫切需要通用且可靠的组织测量方法 氧合。 已经提出了许多技术，包括缺氧标记 和氧气微电极。 本提案的主要目标是 首次在人体中直接比较这两种技术 与奥尔胡斯大学医院的研究人员合作进行肿瘤 丹麦奥胡斯。 1992 年 NIH Oxygen 报告中要求进行这样的比较 车间。 我们的缺氧标记物将被注射到患者体内并持续8小时 随后在肿瘤中进行氧电极测量，然后在组织中进行测量 通过免疫组织化学分析进行活检以检测缺氧标记物结合。 这 缺氧标记方法有助于与其他特征进行比较 与治疗反应相关的肿瘤生理学。 一个这样的比较是 对同一活检样本进行的检查会伴随肿瘤细胞的增殖 （Ki-67）。 我们相信缺氧标记技术将有助于 放射和化疗治疗计划；用于组织研究 正常组织病理模型中的氧合；并且，为了关联 缺氧对微区域应激蛋白表达的影响。