ACTIVATION AND REGULATION OF NORMAL AND NEOPLASTIC CELLS

本研究的总体目标是探索 激活和调节正常和肿瘤细胞的功能。 的 研究涉及（a）细胞复制的细胞质控制，（B） 通过非细胞毒性淋巴因子修饰肿瘤细胞性质，（c） 调节淋巴因子的产生和表达 活性，和（d）非免疫生长因子对 免疫反应 第一类研究是基于我们的 观察到丝裂原或白细胞介素激活的正常淋巴细胞 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的细胞核。 我们还发现， 是由肿瘤细胞组成的。 我们建议调查 通过纯化ADR，研究细胞增殖的调节系统， 与细胞核反应的机制，以及 确定ADR，核和抑制系统的异常， 肿瘤细胞 第二类研究是基于这样的前提 通过免疫系统改变肿瘤细胞的功能特性， 介质可能是一种有用的肿瘤治疗形式， 试图杀死肿瘤细胞的策略。 为此，我们 研究淋巴因子抑制肿瘤细胞迁移的能力， 抑制肿瘤细胞与内皮的结合，以及 淋巴因子对肿瘤细胞行为的其他方面的影响。 研究在过去的 两个类别旨在提供对新颖方式的深入了解， 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， 通常不被认为是免疫系统一部分的调节因子 将被调查。 我们实现这一目标的总体方法包括： 负责因子的纯化和表征， 它们的作用机制，可能的改变的调查， 肿瘤状态，并最终试图操纵系统， 他们参与的可能的治疗努力。 人们希望 这些研究将为细胞生长的基本机制提供新的见解 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.