ACTIVATION AND REGULATION OF NORMAL AND NEOPLASTIC CELLS

这项拟议研究的总体目标是探索 正常细胞和肿瘤细胞的功能激活和调节。这个 研究涉及(A)细胞复制的细胞质控制，(B) 非细胞毒性淋巴因子对肿瘤细胞特性的修饰 淋巴因子的产生和表达的调节 活性，以及(D)非免疫性生长因子对 免疫反应。第一类研究是基于我们的 有丝分裂原或白细胞介素化正常淋巴细胞的观察 含有一种细胞质蛋白(ADR)，可以诱导DNA合成 在无细胞系统中分离出的细胞核。我们还发现，这个因素 是由肿瘤细胞持续产生的。我们建议调查 这种通过提纯ADR来调节细胞增殖的系统，研究 涉及其与细胞核反应的机制，以及 检测ADR、核和抑制系统的异常 肿瘤细胞。第二类研究的前提是 免疫学对肿瘤细胞功能特性的修饰 介体可能是一种有用的肿瘤治疗形式，就像更常见的 有人设计了杀死肿瘤细胞的尝试策略。为此，我们正在 淋巴因子抑制肿瘤细胞迁移能力的研究 抑制肿瘤细胞与血管内皮细胞的结合 淋巴因子对肿瘤细胞其他方面行为的影响。过去的研究 有两个类别旨在提供对以下新方式的洞察 可以实现免疫调节，特别注意淋巴因子 淋巴因子活性的产生和表达。为此，各种 免疫调节大分子以及激素生长和 通常不被认为是免疫系统一部分的调节因子 将会被调查。我们实现这一目标的总体方法包括 负责因素的提纯和表征，阐明 他们的作用机制，调查可能的变化 肿瘤状态，并最终试图操纵系统 他们参与其中，为可能的治疗努力。人们希望， 这些研究将为深入了解细胞生长的基本机制提供帮助 和监管。

The overall goal of the proposed research is to explore mechanisms of activation and regulation of function in normal and neoplastic cells. The studies involve (a) cytoplasmic control of cell replication, (b) modification of tumor cell properties by non-cytotoxic lymphokines, (c) regulation of lymphokine production and the expression of lymphokine activity, and (d) the effects of non-immunologic growth factors on the immune response. Studies in the first category are based on our observation that mitogen- or interleukin-activated normal lymphocytes contain a cytoplasmic protein (ADR) that can induce DNA synthesis in isolated nuclei in a cell-free system. We have also found that this factor is produced consitutively by neoplastic cells. We propose to investigate this regulatory system for cell proliferation by purifying ADR, studying the mechanisms involved in its reaction with the cell nucleus, and determining the abnormalities of ADR, nucleus, and inhibitory systems in neoplastic cells. Studies in the second category are based on the premise that modification of functional properties of tumor cells by immunologic mediators may be as useful a form of tumor therapy as the more commonly attempted strategies desighed to kill tumor cells. To this end, we are studying the ability of lymphokines to inhibit tumor cell migration and inhibit binding of tumor cells to endothelium, as well as the effects of lymphokines on other aspects of tumor cell behavior. Studies in the last two categories are designed to provide insight into novel ways in which immune regulation may be achieved, with special attention to lymphokine production and the expression of lymphokine activity. To this end, various immunologic regulatory macromolecules as well as hormonal growth and regulatory factors not generally considered to be part of the immune system will be investigated. Our overall approach for this aim involves the purification and characterization of responsible factors, elucidation of their mechanism of action, investigation of possible alterations in neoplastic states, and, ultimately, attempts to manipulate the systems in which they participate for possible therapeutic effort. It is hoped that these studies will provide insights into basic mechanisms of cell growth and regulation.