HISTOCHEMICAL MARKERS OF TUMOR HYPOXIA

肿瘤缺氧的组织化学标志物

• 批准号: 3195602
• 负责人: JAMES ARTHUR RALEIGH
• 金额: $ 18.05万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-02-01 至 1993-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3195602
• 关键词: antibody formation; autoradiography; binding proteins; biomarker; biotransformation; cytotoxicity; dogs; host neoplasm interaction; hypoxia; immunocytochemistry; immunofluorescence technique; immunoglobulin G; neoplasm /cancer radiation therapy; peroxidases; radiation recovery; radiation sensitivity; redoxin

The long term objective of the proposed research is to develop a clinically useful measure of tumor hypoxia. Tumor hypoxia can compromise the effectiveness of radiation treatment because of the well-known radioresistance of hypoxic cells. Tumor hypoxia is also seen as a target for selective chemotherapy with hypoxic cell cytotoxins. Rational intervention directed at hypoxic cells using hyperbaric oxygen, hypoxic cell radiosensitizers or hypoxic cell cytotoxins is confounded by the absence of a practical way of measuring hypoxia in individual tumors in particular patients. This grant proposes that hypoxic cell markers can serve this purpose. In the absence of oxygen, cellular redox enzymes activate nitroaromatic compounds in a way which leads to their irreversible binding to cellular proteins. The bound molecules becomes markers of cellular hypoxia. When suitably labelled, the markers can be detected by autoradiography, gamma ray scintigraphy, positron emission tomography, magnetic resonance spectroscopy or immunohistochemistry. In the immunohistochemical approach proposed, fluorescent antibody reagents clamp onto a marker molecule bound to cellular protein. The presence of hypoxia in sections of tumor tissue is then revealed upon fluorescence microscopic examination. The feasibility of using this approach to measure tumor hypoxia has been established in preliminary studies. The specific aims of the proposed research include optimizing the immunohistochemical approach for application in tumors of canine patients with a view to establishing a basis for early clinical application of immunohistochemistry to the measure of tumor hypoxia on an individual tumor basis.

拟议研究的长期目标是开发一种临床上的 肿瘤缺氧的有效量度。肿瘤缺氧会损害 放射治疗的有效性是因为众所周知 低氧细胞的辐射抗性。肿瘤缺氧也被视为目标 用于使用低氧细胞毒素进行选择性化疗。理性 高压氧对低氧细胞的干预作用 细胞放射增敏剂或缺氧细胞毒素被 缺乏一种实用的方法来测量个体肿瘤中的缺氧 特定的病人。这项研究表明，缺氧细胞标记物可以 服务于这一目的。在没有氧气的情况下，细胞内的氧化还原酶 以一种导致硝基芳香族化合物不可逆的方式激活它们 结合到细胞蛋白质上。结合的分子成为标记 细胞缺氧。当适当标记时，可以通过以下方式检测标记 放射自显影，伽马射线闪烁，正电子发射断层扫描， 磁共振波谱或免疫组织化学。在 提出免疫组织化学方法，荧光抗体试剂钳 与细胞蛋白质结合的标记分子上。低氧的存在 然后在荧光显微镜下显示肿瘤组织的切片 考试。用这种方法测量肿瘤的可行性 低氧已在初步研究中得到证实。的具体目标 建议的研究包括优化免疫组织化学方法。 在犬肿瘤中的应用，以期建立一种 为早期临床应用免疫组织化学方法进行检测奠定基础 在单个肿瘤的基础上发现肿瘤缺氧的可能性。