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HYPERTHERMIA AND CELL CYCLE KINETICS OF ERYTHROLEUKEMIA

红白血病的热疗和细胞周期动力学

基本信息

批准号：
3178110
负责人：
GARY VAN ZANT
金额：
$ 12.15万
依托单位：
TEXAS TECH UNIVERSITY HEALTH SCIS CENTER
依托单位国家：
美国
项目类别：
财政年份：
1984
资助国家：
美国
起止时间：
1984-08-01 至 1987-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3178110
关键词：
Friend virus cell cycle cell differentiation cell growth regulation cell population study disease /disorder model erythroleukemia flow cytometry mathematical model neoplasm /cancer thermotherapy viral leukemogenesis

项目摘要

Therapeutic heating of malignant tissue holds promise as an adjunctive modality in cancer treatment. To this end, a thorough knowledge of hyperthermic effects on cell cycle is crucial, both in the context of normal tissue to be spared from lethal effects, and for synergy of hyperthermia with other treatments which fare optimally at various stages of the cell cycle. Established cell lines, with many of the characteristics of neoplastic tissue, have been utilized to study the effects of hyperthermia on cell cycle progression. At best, such populations resemble only the most malignant and undifferentiated types of neoplasm. In addition, these experiments have usually focused on cell death as an endpoint. However, it must be stressed that in developing hyperthermia as an adjunctive therapeutic modality in oncology, it is necessary to establish the greatest possible ratio between lethal effects on malignant versus normal tissue. The usefulness of hyperthermia in cancer treatment may ultimately reside in its sublethal effects. We propose an entirely new approach to study the effects of sublethal hyperthermia on cell cycle kinetics. As opposed to using an established cell line, we will study the effects of heating on virus-transformed erythroid cells which continue to respond to the physiologic regulator of erythropoiesis, erythropoietin. This system will permit not only the analysis of hyperthermic effects on proliferating cells, as has been accomplished in the past, but also the study of hyperthermic perturbations on hormone-regulated differentiation within a homogeneous cell population. We will use flow cytometry to analyze DNA content, erythroid differentiation antigen density (recognized by monoclonal antibodies), and cell size over the course of proliferation and differentiation of Friend virus complex-induced erythroleukemia, as regulated by erythropoietin. Then we will study time-temperature effects on these parameters, principally in the sublethal range of cell heating. We will collect data on control and heat-perturbed cells in a correlated manner so that we can construct a mathematical model, in the form of continuity equations, to describe cellular responses in a multidimensional parameter space. This approach will foster an understanding of cell heating effects in terms of a continuous biological process, and may be applicable in the prediction of hyperthermic effects on renewing cell populations during the course of cancer treatment.

恶性组织的治疗性加热有望成为一种有效的治疗方法。癌症治疗的方式。为此，全面了解高温对细胞周期的影响是至关重要的，无论是在背景下，正常组织免于致命的影响，并协同热疗与其他在不同阶段表现最佳的治疗方法细胞周期。已建立的细胞系中，肿瘤组织的特征，已被用于研究高温对细胞周期进程的影响。最好的情况下，人群只类似于最恶性和未分化的类型，肿瘤。此外，这些实验通常集中在细胞死亡是终点。然而，必须强调，在发展中，热疗作为肿瘤学中一种连续性治疗方式，必须建立最大的可能比率之间的致命影响恶性组织和正常组织的对比热疗在癌症治疗可能最终取决于其亚致死效应。我们提出了一种全新的方法来研究亚致死的影响，热疗对细胞周期动力学的影响而不是使用一个既定的细胞系，我们将研究加热对病毒转化的影响。红系细胞继续响应生理调节剂，促红细胞生成素该系统不仅允许分析高温对增殖细胞的影响，如在过去完成的，但也研究高温扰动在同质细胞群中的细胞分化。我们将使用流式细胞仪分析DNA含量，红细胞，分化抗原密度（由单克隆抗体识别），和 Friend增殖和分化过程中的细胞大小病毒复合物诱导的红白血病，由促红细胞生成素调节。然后我们将研究时间-温度对这些参数的影响，主要是在细胞加热的亚致死范围内。我们将收集数据在控制和热扰动细胞以相关的方式，以连续性方程的形式构建数学模型，描述多维参数空间中的细胞反应。这这种方法将促进对细胞加热效应的理解，连续的生物过程，并可能适用于预测热效应的更新细胞群体的过程中，癌症治疗