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 组织缺氧与心脏病发作，中风和癌症有关，可能是 糖尿病和酒精引起的肝病的关键因素。 癌症 专家长期以来一直对组织缺氧感兴趣，因为缺氧 细胞由于自由基化学的改变而受到放射性抗药性，并且 化学耐药性应在AT或 接近药物扩散的极限。 从更积极的角度来看，低氧肿瘤 细胞可能是通过生物补充策略改善治疗的靶标。 最后，缺氧（或缺氧/再灌注）现在被认为是应力 导致在正常组织和肿瘤组织中的基因表达，这可能是有益的 或有害取决于情况。 正常组织和肿瘤组织中对缺氧的兴趣提高 迫切需要用于测量组织的多功能和可靠方法 氧合。 已经提出了许多技术包括缺氧标记 和氧微电极。 本提议的主要目标是 进行人类的这两种技术之间的第一个直接比较 肿瘤与Aarhus大学医院的调查员合作 丹麦的奥尔胡斯。 在1992年NIH氧气中需要进行这种比较 车间。 我们的缺氧标记将注入患者和8小时 后来在肿瘤中进行的氧电极测量结果 通过免疫组织化学分析对缺氧标记结合的活检。 这 缺氧标记方法可以与其他特征进行比较 与治疗反应有关的肿瘤生理学。 一个这样的比较 在相同的活检样品上进行的将使用肿瘤细胞增殖 （KI-67）。 我们认为低氧标记技术将在 放射和化学疗法治疗计划；用于组织的研究 正常组织病理模型中的氧合；并与之相关 在微区域基础上表达应激蛋白的缺氧。