Radiation-Induced Tumor Cell Migration

辐射诱导的肿瘤细胞迁移

• 批准号: 9796514
• 负责人: EDWARD E GRAVES
• 金额: $ 3.62万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2020-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9796514
• 关键词: Age; Animals; Biomedical Research; Blood specimen; Cancer Biology; Cancer Patient; Cells; Clinic; Communities; Data; Development; Disease; Family; First Generation College Students; Funding; Gastrointestinal Neoplasms; Goals; Granulocyte-Macrophage Colony-Stimulating Factor; Growth; Human; Immune; In Vitro; Knowledge; Latino; Lead; Lesion; Location; Lung; Lung Neoplasms; Mammary Neoplasms; Molecular; Molecular Analysis; Neoplasm Circulating Cells; Parents; Process; Radiation; Radiation Dose Unit; Radiation therapy; Recurrence; Research; Research Personnel; Schools; Science; Site; Structure of parenchyma of lung; System; Technology; Time; Tissue Harvesting; Tumor Cell Migration; United States; Universities; cancer therapy; career; cell killing; clinically relevant; clinically significant; college; cytokine; doctoral student; experimental study; improved; in vivo; macrophage; mouse model; neoplastic cell; novel; programs; radiation effect; radiation response; recruit; response; targeted treatment; tumor

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.

项目摘要 这个R 01多样性补充的目标是支持Luis Soto博士的持续发展。学生 斯坦福大学癌症生物学博士课程，因为他完成了博士研究，并走向职业生涯 在生物医学研究中。路易斯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 拉丁裔的遗产使他成为生物医学研究界的一个独特的补充。这位家长的 要求补充的重点是了解辐射调节肿瘤的机制 细胞迁移及其在肿瘤治疗中的临床意义。从历史上看，辐射的功效 治疗已经根据在照射区域内被杀死的细胞的数量来量化， 当达到一定数量的细胞杀伤时，肿瘤被认为发生了。但据 越来越多地认识到辐射可以产生局部和全身的继发性影响， 可以部分增强或抑制辐射对肿瘤细胞的杀伤。我们最近在体外和体内都显示了 在治疗时迁移辐射野外的循环肿瘤细胞（CTC）的体内系统 因此不受其影响的肿瘤可以在受辐射刺激的过程中返回到母体病变。在我们 R 01项目，我们正在研究这个过程中使用新的小鼠模型的放射治疗和肿瘤细胞 迁移，辐射诱导的粒细胞巨噬细胞集落刺激因子（GM-CSF）的分子分析， 抑制这一过程的靶向治疗，以及从人类癌症患者收集的血液样品的分析 接受放射治疗作为补充的一部分，路易斯将进行的研究将评估辐射 正常肺组织的反应，该部位通常在治疗期间接受中等剂量的辐射 靶向肺乳腺和胃肠道肿瘤。路易斯收集的初步数据显示， CTCs的照射肺增加，表明辐射刺激迁移的吸引和/或生长， 肿瘤细胞Luis将应用肿瘤细胞迁移和放射治疗的新型小鼠模型来研究这一过程， 阐明其分子和细胞基础。然后，他将评估临床相关疗法抑制 这个过程，随后可以在临床上与放射治疗相结合，以提高疗效。 放疗因此，本R 01补充材料将提供有关中学的重要基础知识 辐射的影响，同时促进路易斯的发展成为一个独立的调查员。