SIMULATED TUMOR THERAPY WITH AN IN VITRO MODEL

体外模型模拟肿瘤治疗

• 批准号: 3175584
• 负责人: RALPH E. DURAND
• 金额: $ 8.07万
• 依托单位: BRITISH COLUMBIA CANCER AGENCY
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-07-01 至 1987-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3175584
• 关键词: biological models; cellular oncology; combination cancer therapy; neoplasm /cancer chemotherapy; neoplasm /cancer radiation therapy; radiation sensitivity; respiratory oxygenation; tissue /cell culture

We will evaluate the hypothesis that greater antitumor effects can be achieved by appropriately sequencing selected drugs with radiation treatments. The V79 multicell spheroid tumor model is our choice for these studies, since it presents many of the same "drug delivery" problems of solid tumors, spontaneously develops both non-cycling and hypoxic cell populations, yet grows in an environment that can be precisely controlled and reproduced. We will define effective drugs as those capable of diffusing into the spheroid, and inactivating cells in that tumor-like environment. This will be determined by our recently-developed techniques of fluorescence-activated cell sorting to selectively recover cells from any desired depth of the spheroids; the sorted cells can be assayed for clonogenicity to determine the activity of the drugs, and whether they interact with radiation. We will further determine whether such interaction(s) are cell cycle or oxygen related, and attempt to exploit them in multifraction exposures. We also intend to evaluate whether flow cytometry techniques for monitoring several indicators of cell function following treatment (eg, cell cycle redistribution, mitochondrial function, DNA synthesis rate, or thiol content) can suggest optimum timing for subsequent treatment in multifraction regimens, and perhaps predict the eventual outcome. We anticipate that our results will identify relevant therapeutic regimens, provide insight into basic mechanisms of drug-radiation interactions, and potentially lead to prognostic tests which may prove valuable during human tumor therapy.

我们将评估这样的假设：更大的抗肿瘤作用可以是 通过对选定的药物进行适当的放射测序来实现 治疗。 V79 多细胞球状肿瘤模型是我们针对这些疾病的选择 研究，因为它提出了许多与 实体瘤自发产生非循环细胞和缺氧细胞 人口，但在可以精确控制的环境中生长 并转载。 我们将有效的药物定义为那些能够 扩散到球体中，并使肿瘤样细胞失活 环境。 这将由我们最近开发的技术决定 荧光激活细胞分选以选择性地回收细胞 任何所需的球体深度；可以对分选的细胞进行分析 克隆形成性来确定药物的活性，以及​​它们是否 与辐射相互作用。 我们将进一步确定是否存在此类情况 相互作用与细胞周期或氧气相关，并尝试利用 他们在多重曝光中。 我们还打算评估流量是否 用于监测细胞功能多项指标的细胞计数技术 治疗后（例如，细胞周期重新分配、线粒体功能、 DNA 合成率（或硫醇含量）可以建议最佳时机 多分次治疗方案中的后续治疗，也许可以预测 最终结果。 我们预计我们的结果将确定相关的 治疗方案，提供对基本机制的深入了解 药物-放射相互作用，并可能导致预后测试 在人类肿瘤治疗过程中可能被证明是有价值的。