Defining the Cellular Target of Radiation Therapy
定义放射治疗的细胞靶点
基本信息
- 批准号:8638098
- 负责人:
- 金额:$ 20.49万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2014
- 资助国家:美国
- 起止时间:2014-01-01 至 2015-12-31
- 项目状态:已结题
- 来源:
- 关键词:AdenovirusesAnimalsApoptosisCancer BiologyCancer ControlCancer PatientCell DeathCellsDNA DamageDextransEndothelial CellsExtravasationFoundationsFutureGene-ModifiedGenesGenetically Engineered MouseGoalsIn VitroInjuryKnowledgeLeadLungMalignant NeoplasmsMalignant neoplasm of lungMediatingMissionMolecular WeightMusMutateMyocardialNational Cancer InstituteNon-Small-Cell Lung CarcinomaNormal tissue morphologyPathway interactionsPatientsPlayPopulationPrimary NeoplasmPublic HealthRadiationRadiation ToleranceRadiation therapyRadiobiologyRelative (related person)ResearchResearch SupportRoleStromal CellsSystemTargeted RadiotherapyTechnologyVascular PermeabilitiesWorkcadherin 5cancer therapycellular targetingclinical caredesigndextrangastrointestinalimprovedin vivoinnovationinsightirradiationkillingslung sarcomamouse modelneoplastic cellnovelnovel strategiespublic health relevancerecombinaseresponsesarcomasoft tissuetooltumortumor growthtumor microenvironment
项目摘要
DESCRIPTION (provided by applicant): Radiation therapy is utilized to treat approximately 50% of all patients with cancer. However, a fundamental gap in improving the efficacy of radiation therapy is that the mechanisms by which radiotherapy controls tumors remain poorly understood. For example, it is controversial whether tumor endothelial cells are a critical target of radiation therapy, which mediate tumor cure. The overall goal of this research is to define the cellular target of radiation therapy: tumor cells (referred to here as tumor parenchymal cells) vs.
endothelial cells. The central hypothesis of this application is that radiation therapy cures cance by killing tumor parenchymal cells rather than tumor endothelial cells. To study the relative contribution of tumor endothelial cells and tumor parenchymal cells as targets of radiation therapy, we have generated novel genetically engineered mice. Previously, we used Cre recombinase to develop genetically engineered mouse models of lung cancer and soft tissue sarcoma to study radiation biology. We have now generated novel strains of genetically engineered mice in which primary cancers can be generated with Flp recombinase. In this system, Cre recombinase can still be utilized to modify genes specifically in tumor endothelial cells. Utilizing Flp and Cre recombinases (ie dual recombinase technology) to study the role of tumor endothelial cells in radiation therapy is highly innovative because primary cancers can be initiated with one recombinase, while the other recombinase can be utilized to specifically modify the radiosensitivity of the endothelial cells. The proposed research is significant, because it will clarify whether tumor endothelial cells are a critical target for radiation therapy Ultimately, such knowledge has the potential to lay the foundation for novel approaches to improve the efficacy of radiation therapy.
描述(由申请人提供):放射治疗用于治疗约50%的癌症患者。然而,在提高放射治疗的疗效方面的一个根本差距是,放射治疗控制肿瘤的机制仍然知之甚少。例如,肿瘤内皮细胞是否是介导肿瘤治愈的放射治疗的关键靶点是有争议的。本研究的总体目标是确定放射治疗的细胞靶点:肿瘤细胞(此处称为肿瘤实质细胞)与
内皮细胞该应用的中心假设是放射疗法通过杀死肿瘤实质细胞而不是肿瘤内皮细胞来治愈癌症。为了研究肿瘤内皮细胞和肿瘤实质细胞作为放射治疗靶点的相对贡献,我们产生了新型基因工程小鼠。以前,我们使用Cre重组酶开发肺癌和软组织肉瘤的基因工程小鼠模型来研究辐射生物学。我们现在已经产生了新的基因工程小鼠品系,其中原发性癌症可以用Flp重组酶产生。在该系统中,Cre重组酶仍然可以用于特异性修饰肿瘤内皮细胞中的基因。利用Flp和Cre重组酶(即双重组酶技术)来研究肿瘤内皮细胞在放射治疗中的作用是高度创新的,因为原发性癌症可以用一种重组酶启动,而另一种重组酶可以用于特异性地修饰内皮细胞的放射敏感性。这项研究意义重大,因为它将澄清肿瘤内皮细胞是否是放射治疗的关键靶点。最终,这些知识有可能为提高放射治疗疗效的新方法奠定基础。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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David Guy Kirsch其他文献
David Guy Kirsch的其他文献
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{{ truncateString('David Guy Kirsch', 18)}}的其他基金
Advancing Cancer Therapy through Groundbreaking Research in Radiation Biology
通过放射生物学的突破性研究推进癌症治疗
- 批准号:
10517545 - 财政年份:2016
- 资助金额:
$ 20.49万 - 项目类别:
Advancing Cancer Therapy through Ground Breaking Research in Radiation Biology
通过放射生物学的突破性研究推进癌症治疗
- 批准号:
10064609 - 财政年份:2016
- 资助金额:
$ 20.49万 - 项目类别:
Advancing Cancer Therapy through Ground Breaking Research in Radiation Biology
通过放射生物学的突破性研究推进癌症治疗
- 批准号:
10323262 - 财政年份:2016
- 资助金额:
$ 20.49万 - 项目类别:
Advancing Cancer Therapy through Ground Breaking Research in Radiation Biology
通过放射生物学的突破性研究推进癌症治疗
- 批准号:
8956241 - 财政年份:2016
- 资助金额:
$ 20.49万 - 项目类别:
Advancing Cancer Therapy through Ground Breaking Research in Radiation Biology
通过放射生物学的突破性研究推进癌症治疗
- 批准号:
9581606 - 财政年份:2016
- 资助金额:
$ 20.49万 - 项目类别:
Advancing Cancer Therapy through Groundbreaking Research in Radiation Biology
通过放射生物学的突破性研究推进癌症治疗
- 批准号:
10873384 - 财政年份:2016
- 资助金额:
$ 20.49万 - 项目类别:
Radiation Therapy: Dissecting the Role of Stromal Cells in Tumor Control
放射治疗:剖析基质细胞在肿瘤控制中的作用
- 批准号:
8578172 - 财政年份:2013
- 资助金额:
$ 20.49万 - 项目类别:
Radiation Therapy: Dissecting the Role of Stromal Cells in Tumor Control
放射治疗:剖析基质细胞在肿瘤控制中的作用
- 批准号:
8843808 - 财政年份:2013
- 资助金额:
$ 20.49万 - 项目类别:
Radiation Therapy: Dissecting the Role of Stromal Cells in Tumor Control
放射治疗:剖析基质细胞在肿瘤控制中的作用
- 批准号:
8705475 - 财政年份:2013
- 资助金额:
$ 20.49万 - 项目类别:
Independent Scientist Award for Radiation Research
辐射研究独立科学家奖
- 批准号:
8220726 - 财政年份:2011
- 资助金额:
$ 20.49万 - 项目类别:
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