Controllability of Stress--Effects on Tumor Development

描述(申请人摘要)：这些研究将考察如何发展 癌症可能会受到压力条件的影响，这些压力条件是可以控制的 与无法控制形成对比，并试图阐明 压力会影响肿瘤的发展。在计算机上施加控制的能力 压力状况对于决定人的压力有多大是非常重要的 情境可能是最重要的行为/心理 到目前为止已经发现的对压力的影响。为了这些 采用了研究、动物模型和实验诱导的肿瘤： 建议的研究使用Fisher 344大鼠的同基因MADB 106肿瘤 和WAG大鼠同基因的CC53-1肿瘤。拟议的项目旨在 为了继续Jay Weiss博士的实验室之间正在进行的合作 行为/生理心理学家和精神病学教授 埃默里大学和罗纳德·戈德法布博士的行为科学， 癌症研究所所长兼癌症研究所所长 北得克萨斯大学分子生物学和免疫学。近期工作 发现了一些令人惊讶的新发现 对上述肿瘤的调控。早期的研究表明，增长 这些肿瘤是由自然杀伤(NK)细胞控制的。我们最近 研究发现，在确认NK细胞在这方面很重要的同时， 提示B淋巴细胞在这一过程中起着重要作用。我们发现 B淋巴细胞在肿瘤发生部位短时间内积聚 肿瘤细胞被引入后的时间和免疫中和研究 表明B淋巴细胞的活动在肿瘤后不久就发生了 细胞的存在对于抵御肿瘤的发展非常重要。就目前而言 由于B淋巴细胞对应激条件高度敏感，因此应激效应 B淋巴细胞可能是压力影响癌症的一个重要方面 发展。 拟议的研究将确定控制一个 应激源与非控制性因素对(1)肺癌发生的影响 以及(2)聚集在上述部位的淋巴细胞亚型 肿瘤生长，以及(3)评估B淋巴细胞和 由于对照和非对照产生差异的循环类固醇。 进一步测试了B淋巴细胞在抵抗肿瘤中的作用 通过组织学和组织学方法检测(1)淋巴细胞与肿瘤细胞的相互作用 电子显微镜技术和(2)B淋巴细胞过继转移。 最后，这些方法将通过评估控制与 非控制性影响淋巴细胞-肿瘤细胞相互作用的组织学研究 分析。

DESCRIPTION (applicant's abstract): These studies will examine how development of cancer can be affected by stressful conditions that are controllable in contrast to uncontrollable, and attempt to shed light on the mechanism by which stress can affect tumor development. The ability to exert control in a stressful situation is highly important for determining how stressful the situation is, being perhaps the most important behavioral/psychological influence on stress that has been discovered up to this time. For these studies, animal models and experimentally-induced tumors are employed: the proposed studies use the MADB 106 tumor that is syngeneic in Fisher 344 rats and the CC53 1 tumor that is syngeneic in WAG rats. The proposed project seeks to continue an ongoing collaboration between the laboratory of Dr. Jay Weiss, a behavioral/physiological psychologist and Professor of Psychiatry and Behavioral Sciences at Emory University, and that of Dr. Ronald Goldfarb, Director of the Institute for Cancer Research and Chairman of the Department of Molecular Biology and Immunology at the University of North Texas. Recent work of this collaborative group has revealed surprising new findings relating to regulation of the tumors indicated above. Earlier studies had shown that growth of these tumors was controlled by natural killer (NK) cells. Our recent findings, while confirming that NK cells are important in this regard, also indicate that B lymphocytes play an important role in this process. We found that B lymphocytes accumulate at the site of tumor development within a short time after tumor cells are introduced, and immunoneutralization studies indicate that actions of B lymphocytes occurring very soon after the tumor cells are present are important in defense against tumor development. Insofar as B lymphocytes are highly responsive to stressful conditions, stress effects on B lymphocytes may be an important aspect of how stress can affect cancer development. The proposed studies will determine the consequences of having control over a stressor vs. non-control on (1) lung tumor development using the models described above and (2) lymphocyte subtypes that accumulate at the site of tumor growth, and also (3) evaluate the possible role of B lymphocytes and circulating steroids in producing differences due to control vs. non-control. Further testing of the role of B lymphocytes in defense against tumor is done by examining (1) lymphocyte-tumor cell interaction using histological and electron microscopic techniques and (2) adoptive transfer of B lymphocytes. Finally, these approaches will be combined by assessing how control vs. non-control affects lymphocyte-tumor cell interaction assessed by histological analysis.