CELL PROLIFERATION KINETICS IN HEMATOPOIETIC TUMORS

本申请的总体目标大体上保持不变。 即：1）对重点增殖型 不同类型的人造血系统肿瘤中肿瘤细胞的参数， 将这些与细胞标志物研究和临床特征相关联， 确定与治疗成功相关的因素，或 失败; 2）确定选定的细胞毒性药物对正常人的影响 和肿瘤性人类造血细胞在短期培养物中， 建立文化，以开发改善治疗的线索， 3）克隆祖细胞的纯化、分离和鉴定 正常人血液和骨髓中的细胞，并比较它们的增殖 慢性粒细胞性白血病中克隆祖细胞的动力学 白血病（CML）和其他造血系统肿瘤; 4）完善 冻存造血干细胞自体移植 从预后不良患者的骨髓和/或血液中获得 淋巴瘤和其他选定的肿瘤治疗前，用于挽救 这些患者接受了旨在根除肿瘤的积极化疗， 肿瘤 我们还在研究净化骨髓的改进方法， 残留的肿瘤细胞，使用细胞毒性药物或单克隆抗体; 5） 开发用于动力学分析的改进的流动显微荧光测定程序， 改进的数学模型，更准确和现实地定义 正常和肿瘤细胞群的动力学行为以及 他们之间的互动。 预计，提高认识 肿瘤细胞在不同造血系统中的动力学行为 肿瘤和治疗引起的动力学扰动将允许 为每一个人开发更个性化和更有效的治疗方法 特定疾病实体。 这将需要更全面的知识， 各种肿瘤的细胞起源，更准确的分类， 分期技术，关键预后因素的更清晰定义，以及 更好地了解增殖行为的变异性， 在任何给定的肿瘤类别内对治疗的反应性。

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.