Controllability of Stress--Effects on Tumor Development

描述（申请人摘要）：这些研究将研究如何开发 癌症的发病率可能会受到压力的影响，这些压力是可以控制的， 与无法控制的形成对比，并试图阐明 压力会影响肿瘤发展。在一个人的生命中， 紧张的情况是非常重要的，以确定如何紧张， 情况是，也许是最重要的行为/心理 到目前为止已经发现的对应力的影响。为这些 使用了研究、动物模型和实验诱导的肿瘤： 提出的研究使用在Fisher 344大鼠中同源的MADB 106肿瘤 以及WAG大鼠中同源的CC 53 1肿瘤。拟议项目寻求 继续杰伊韦斯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， 埃默里大学的行为科学，以及罗纳德戈德法布博士， 癌症研究所所长和癌症研究系主任 分子生物学和免疫学在北德克萨斯大学。最近的工作 这个合作小组的成员揭示了令人惊讶的新发现， 调节上述肿瘤。早期的研究表明， 这些肿瘤中的大多数是由自然杀伤（NK）细胞控制的。我们最近 研究结果，虽然证实NK细胞在这方面很重要， 表明B淋巴细胞在此过程中起重要作用。我们发现 B淋巴细胞在短时间内聚集在肿瘤发展部位， 引入肿瘤细胞后的时间，以及免疫中和研究 表明B淋巴细胞在肿瘤发生后很快就发生作用 细胞在防御肿瘤发展中起重要作用。只要 由于B淋巴细胞对应激条件高度敏感， 可能是压力如何影响癌症的重要方面 发展 拟议中的研究将确定控制一个 应激物与非对照对（1）使用模型的肺肿瘤发展的影响 （2）淋巴细胞亚型，其聚集在 肿瘤生长，以及（3）评估B淋巴细胞的可能作用， 由于对照组与非对照组，循环类固醇产生差异。 进一步测试B淋巴细胞在防御肿瘤中的作用 通过检查（1）淋巴细胞-肿瘤细胞的相互作用， （2）B淋巴细胞过继转移。 最后，这些方法将通过评估控制与 非对照影响通过组织学评估的淋巴细胞-肿瘤细胞相互作用 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.