PHYSIOLOGIC DETERMINANTS OF HYPERTHERMIC TUMOR RESPONSE

肿瘤热反应的生理学决定因素

• 批准号: 3180294
• 负责人: JOSEPH J. H. ACKERMAN
• 金额: $ 24.79万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-30 至 1993-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3180294
• 关键词: acidity /alkalinity; adenosine triphosphate; blood viscosity; cancer registry /resource; cell biology; cell growth regulation; cell population study; cellular oncology; clone cells; deoxyglucose; genetic strain; high performance liquid chromatography; hyperglycemia; hyperthermia therapy; hypoxia; laboratory mouse; lactates; neoplasm /cancer blood supply; neoplasm /cancer thermotherapy; neoplasm /cancer transplantation; neoplastic cell; noninvasive diagnosis; nuclear magnetic resonance spectroscopy; physiology; radiotracer

The main objective of this application is to examine the role of tumor physiology in the therapeutic response of solid tumors to hyperthermia. In specific, the following interactions will be examined. a) The relationship between pretreatment tumor physiologic status and therapeutic response to heat. b) The effect of thermal sensitivity modulators (i.e., hyperglycemia or flavone acetic acid) on pretreatment tumor physiologic status and the effect of those changes on therapeutic response to heat. c) The effect of heat on tumor physiological status both during and after heating and the effect of the heat induced modulation of such metabolic status on therapeutic response. These complex interactions between tumor physiological status and therapeutic response. These complex interactions between tumor physiological status and therapeutic response to hyperthermia will be examined in a set of parallel in situ/in vitro experiments. In the in situ experiments, the pretreatment tumor physiological status and its dynamic response to thermal sensitizers and hyperthermia (at 41 degrees C, 43 degrees, or 45 degrees C) and the relationship of that physiological status to therapeutic response will be examined with multinuclear in vivo NMR spectroscopy; (i.e., 31P NMR will be used to measure tumor pH and the concentrations of ATP, PCr and Pi; 1H NMR will be used to measure tumor lactate concentration; and a 2H NMR technique recently developed and validated in the PI's laboratory will be used to measure tumor blood flow.) In a parallel set of in vitro experiments, the interrelated physiological variables will be independently controlled in an in vitro perfusion apparatus which allows the physiologic status of the cells to be monitored continuously and noninvasively with 31P and 1H NMR. Because these interactions may have an impact on the optimum sequencing and timing of hyperthermia when used as an adjuvant to either radiotherapy or chemotherapy and NMR spectroscopy can be used to examine human tumors, the results of these laboratory investigations should provide a framework for the implementation of NMR spectroscopy to aid in the clinical application of hyperthermia alone and in conjunction with other modalities of therapy.

该应用程序的主要目的是检查 实体瘤治疗反应中的肿瘤生理学 高热。 具体而言，将进行以下交互 检查了。 a) 与预处理肿瘤的关系 生理状态和对热的治疗反应。 b) 效果 热敏调节剂（即高血糖或黄酮 醋酸）对治疗前肿瘤生理状态的影响 这些变化对热治疗反应的影响。 c) 的 热对术中和术后肿瘤生理状态的影响 加热和热诱导调制的影响 代谢状态对治疗反应的影响。 这些复杂的 肿瘤生理状态与治疗之间的相互作用 回复。 肿瘤生理学之间的这些复杂的相互作用 将检查热疗的状态和治疗反应 在一组平行的原位/体外实验中。 在原地 实验、治疗前肿瘤的生理状态及其 对热敏剂和高热的动态响应（41 摄氏度、43 摄氏度或 45 摄氏度）以及以下关系： 将检查治疗反应的生理状态 具有体内多核核磁共振波谱； （即 31P NMR 将是 用于测量肿瘤pH值以及ATP、PCr和Pi的浓度； 1H NMR将用于测量肿瘤乳酸浓度；和一个 最近开发并在 PI 中验证的 2H NMR 技术 实验室将用于测量肿瘤血流量。） 平行的体外实验组，相互关联的 生理变量将在一个in中独立控制 体外灌注装置，允许生理状态 使用 31P 连续、无创地监测细胞 和 1H NMR。 因为这些相互作用可能会影响 用作热疗时的最佳顺序和时机 放疗或化疗和 NMR 的辅助治疗 光谱学可用于检查人类肿瘤，其结果 这些实验室调查应提供一个框架 核磁共振波谱技术的实施有助于临床 单独应用热疗或与其他方法联合应用 治疗方式。