Radiation-Induced Tumor Cell Migration

项目摘要 这个R01多样性补充的目的是为了支持Luis Soto的持续发展，Luis Soto是一名 斯坦福癌症生物学博士项目，随着他完成博士研究并迈向职业生涯 在生物医学研究方面。路易斯在12岁时移民到美国，随后成为美国公民， 他是家里第一个既上大学又读研究生的人。他的第一代学生身份以及他的 拉丁裔血统使他成为生物医学研究界的独一无二的新成员。此操作所针对的父级Awrd 需要补充的是着重于了解辐射调节肿瘤的机制 细胞迁移及其在癌症治疗中的临床意义。从历史上看，辐射的功效 在对照和/或治愈的情况下，根据照射野内被杀死的细胞数量来量化治疗。 当达到一定数量的细胞杀伤时，肿瘤被认为是发生的。然而，它是 越来越多的人认识到，辐射可产生可在局部和系统内发挥作用的次要影响，并 可部分增强或抑制辐射对肿瘤细胞的杀伤作用。我们最近在体外和体内都展示了 体内系统迁移治疗时在辐射野外的循环肿瘤细胞(CTCs) 因此，在受到辐射刺激的过程中，不受其影响的病变可以返回到母体病变。在我们的 在R01项目的资助下，我们正在使用新的小鼠放射治疗和肿瘤细胞模型来研究这一过程 放射诱导粒细胞巨噬细胞集落刺激因子的迁移、分子分析 抑制这一过程的靶向治疗，以及对人类癌症患者血液样本的分析 正在接受放射治疗。作为本补充的一部分，路易斯将进行的研究将评估辐射 正常肺组织的反应，治疗期间通常接受中等剂量辐射的部位 目标是肺部、乳房和胃肠道肿瘤。路易斯收集的初步数据显示，招募 CTCs对照射后肺组织的趋化作用增加，提示辐射刺激了迁移细胞的吸引和/或生长。 肿瘤细胞。路易斯将应用肿瘤细胞迁移和放射治疗的新小鼠模型来研究这一过程和 阐明其分子和细胞基础。然后，他将评估临床相关疗法的抑制能力 这一过程，随后可以结合临床上的放射治疗，以提高疗效 放射治疗。因此，本R01附录将提供有关次要信息的重要基础知识 辐射的影响，同时促进路易斯向独立调查员的发展。

PROJECT ABSTRACT The goal of this R01 diversity supplement is to support the continued development of Luis Soto, a Ph.D. student in the Stanford Cancer Biology doctoral program, as he completes his doctoral research and moves towards a career in biomedical research. Luis immigrated to the United States at age 12 and subsequently became a citizen, and is the first in his family to attend college as well as graduate school. His first generation student status as well as his Latino heritage makes him a unique addition to the biomedical research community. The parent awrd for which this supplement is requested is focused on understanding the mechanisms through which radiation modulates tumor cell migration and the clinical significance of this phenomenon in cancer therapy. Historically, the efficacy of radiation therapy has been quantified in terms of the number of cells killed within the irradiated field, with control and/or cure of the tumor being considered to occur when a certain number of logs of cell kill are achieved. However, it is increasingly recognized that radiation can exert secondary effects that can act both locally and systemically and may in part enhance or inhibit the killing of tumor cells by radiation. We have recently shown in both in vitro and in vivo systems that migrating circulating tumor cells (CTCs) that were outside the radiation field at the time of treatment and therefore unaffected by it can return to the parent lesion in a process that is stimulated by radiation. In our funded R01 project, we are studying this process using novel mouse models of radiotherapy and tumor cell migration, molecular analyses of radiation-induced granulocyte macrophage colony stimulating factor (GM-CSF), targeted therapies inhibiting this process, and analysis of blood samples collected from human cancer patients undergoing radiotherapy. The research to be conducted by Luis as part of this supplement will evaluate the radiation response of normal lung tissue, a site that commonly receives a moderate dose of radiation during treatments targeting lung, breast, and gastrointestinal tumors. Preliminary data collected by Luis has shown that the recruitment of CTCs to irradiated lung is increased, suggesting that radiation stimulates the attraction and/or growth of migrating tumor cells. Luis will apply novel mouse models of tumor cell migration and radiotherapy to study this process and to elucidate its molecular and cellular basis. He will then evaluate the ability of clinically-relevant therapies to inhibit this process, which could subsequently be combined with radiotherapy in the clinic to improve the efficacy of radiotherapy. This R01 supplement will therefore provide important basic knowledge concerning the secondary effects of radiation while furthering Luis’s development toward an independent investigator.