CELL PROLIFERATION KINETICS IN HEMATOPOIETIC TUMORS

造血肿瘤中的细胞增殖动力学

• 批准号: 3165092
• 负责人: BAYARD D CLARKSON
• 金额: $ 20.6万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 1976
• 资助国家: 美国
• 起止时间: 1976-06-30 至 1987-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3165092
• 关键词: autoradiography; blood fractionation; bone marrow exam; cell growth regulation; clone cells; flow cytometry; hematopoietic stem cells; hematopoietic tissue; human subject; immunotoxicity; lymphoma; mathematical model; membrane activity; multiple myeloma; neoplasm /cancer chemotherapy; neoplasm /cancer classification /staging; neoplasm /cancer diagnosis; neoplastic cell; prognosis; radiotracer

The overall objectives of this application largely remain the same. Namely: 1) To conduct a comprehensive survey of key proliferative parameters of tumor cells in different types of human hematopoietic tumors, to correlate these with cell marker studies and clinical features, and to identify those factors which are associated with therapeutic success or failure; 2) To determine the effects of selected cytotoxic drugs on normal and neoplastic human hematopoietic cells in short-term cultures and in established cultures in order to develop leads for improved therapeutic programs; 3) To purify, isolate and characterize the clonogenic progenitor cells in normal huma blood and marrow and compare their proliferative kinetics with those of clonogenic progenitor cells in chronic myelogenous leukemia (CML) and other hematopoietic tumors; 4) To refine procedures for autologous transplantation for frozen and stored hematopoietic stem cells obtained from the marrow and/or blood of patients with poor prognosis lymphomas and other selected tumors prior to treatment to be used to rescue the patients following aggressive chemotherapy aimed at eradicating the tumor. We are also investigating improved methods for purging marrow of residual tumor cells, using cytotoxic drugs or monoclonal antibodies; 5) To develop improved flow microfluorometric procedures for kinetic analysis and improved mathematical models which more accurately and realistically define the kinetic behavior of normal and tumor cell populations and the interactions between them. It is anticipated that improved understanding of the kinetic behavior of the neoplastic cells in different hematopoietic tumors and of the kinetic perturbations caused by treatment will permit development of more individualized and effective treatment for each specific disease entity. This will require more complete knowledge of the cellular origins of the various tumors, more accurate classification and staging techniques, clearer definition of key prognostic factors, and better appreciation of variability in proliferative behavior and responsiveness to treatment within any given tumor category.

这个应用程序的总体目标基本保持不变。 即：1)对关键的增殖剂进行全面调查 不同类型人造血肿瘤的肿瘤细胞参数， 将这些与细胞标志物研究和临床特征相关联，并 确定那些与治疗成功相关的因素或 未能确定选定的细胞毒药物对正常人的影响 和肿瘤人类造血细胞在短期培养和 建立文化，以开发改进治疗的线索 程序；3)纯化、分离和鉴定克隆前体细胞 正常人血液和骨髓中的细胞及其增殖能力的比较 慢性髓系白血病克隆性祖细胞的动态变化 白血病(CML)和其他造血系统肿瘤；4)完善治疗程序 冷冻保存的造血干细胞的自体移植 取自预后不良患者的骨髓和/或血液 淋巴瘤和其他选定的肿瘤在治疗前将用于抢救 接受积极化疗的患者旨在根除 肿瘤。我们还在研究净化骨髓的改进方法 残留的肿瘤细胞，使用细胞毒药物或单抗；5) 开发改进的流动微量荧光分析方法，用于动力学分析和 改进的数学模型，更准确、更真实地定义 正常细胞和肿瘤细胞群体的运动行为以及 它们之间的互动。预计更好的理解 肿瘤细胞在不同造血系统中的运动行为 肿瘤和由治疗引起的动力学扰动将允许 开发更个性化和更有效的治疗方法 特定疾病实体。这将需要更全面地了解 各种肿瘤的细胞起源，更准确的分类和 分期技术，更清晰地定义关键预后因素，以及 更好地认识到增殖性行为的变异性 对任何给定肿瘤类别内的治疗的反应性。