Engineering sensitive microfluidic multiplex technology for isolating circulating
用于隔离循环的工程敏感微流体多重技术
基本信息
- 批准号:7852275
- 负责人:
- 金额:$ 15.95万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2009
- 资助国家:美国
- 起止时间:2009-09-30 至 2010-08-31
- 项目状态:已结题
- 来源:
- 关键词:AdultBiologic CharacteristicBiologicalBiological MarkersBiologyBloodBone MarrowCellsClinicalCoculture TechniquesColon CarcinomaColorectal CancerDiagnosticDiseaseEngineeringFutureHumanIn VitroIndividualKnowledgeLearningMalignant NeoplasmsMedicalMetastatic CarcinomaMicrofluidicsModelingMolecularNeoplasm MetastasisParticipantPatientsResearchResearch Project GrantsRiskRoleSeedsSoilStagingStem cellsStreamSumTechnologyTherapeuticTumor Volumeabstractingangiogenesisbasecancer stem cellcarcinogenesisimprovedmetastatic processneoplastic cellnovelperipheral bloodprognosticprogramspublic health relevancetherapeutic targettherapy outcometooltranslational approachtreatment planningtumor growthtumor progression
项目摘要
DESCRIPTION (Provided by the applicant)
Abstract: Despite major strides in understanding of the molecular basis of cancer and cancer therapeutics, the complexities of metastatic process remain poorly understood. Especially in colorectal cancer, it has been severely hampered by limited knowledge about the cells that cause the disease to metastasize through the blood stream. Circulating cells of several lineages are thought to participate in angiogenesis, tumor growth and metastasis. Among these, circulating tumor cells (CTCs) shed from the primary and metastatic carcinomas presumably give rise to blood borne metastases, where as circulating endothelial progenitor cells (CEPCs) from adult bone marrow initiating the pre-metastatic niche. Hence the seed (CTCs) and soil (CEPCs) concept. Although current models explain distinct and important aspects of metastasis, no single model can explain the sum of the cellular changes apparent in human cancer progression and metastasis. I will investigate the inextricable relationship between CTCs, and CEPCs, and their roles in carcinogenesis and metastasis. I propose to take a radical, but integrated technology and biology based translational approach using microfluidic engineering tools to identify, and study the biological relevance of these rare cells in peripheral blood. This approach will seek the following (1) Does the levels of CEPCs and CTCs in early and late stages of colon cancer correlate with each other along with tumor volume and clinical course (2) Can dynamic changes in their load during the course of treatment plan can predict the clinical outcome of the therapy (3) Are there any changes to phenotypic and biological characteristics of these cells that distinguish prognostic subtypes (4) What is the effect of CEPCs on CTCs when cocultured and the fundamental biology of interaction (5) Can we expand these cells in vitro to identify the true "metastatic precursors" or "cancer stem cells" and to determine biomarkers of angiogenesis and metastasis as potential therapeutic targets.
Public Health Relevance: There may not be a direct medical benefit to individual participants. However, through this research program, I expect to learn more about novel metastatic markers. Using a novel integrated microfluidic technology, the biological significance of circulating cells in carcinogenesis and metastasis will be investigated. The risks of participating in the research project are reasonable to assume in order to possibly improve diagnostic, prognostic and treatment capabilities for the participants and future patients with cancer.
描述(由申请人提供)
摘要:尽管在理解癌症和癌症治疗的分子基础方面取得了重大进展,但转移过程的复杂性仍然知之甚少。特别是在结直肠癌中,由于对导致疾病通过血流转移的细胞的了解有限,它受到了严重的阻碍。几种谱系的循环细胞被认为参与血管生成、肿瘤生长和转移。其中,从原发性和转移性癌脱落的循环肿瘤细胞(CTC)可能引起血源性转移,而来自成人骨髓的循环内皮祖细胞(CEPC)启动转移前小生境。因此,种子(CTC)和土壤(CEPC)的概念。尽管目前的模型解释了转移的不同和重要方面,但没有一个单一的模型可以解释人类癌症进展和转移中明显的细胞变化的总和。我将研究CTC和CEPC之间不可分割的关系,以及它们在癌发生和转移中的作用。我建议采取一种激进的,但集成的技术和生物学为基础的翻译方法,使用微流体工程工具来识别,并研究这些罕见的细胞在外周血中的生物学相关性。该方法将寻求以下内容:(1)结肠癌早期和晚期的CEPC和CTC水平是否与肿瘤体积和临床病程相互沿着?(2)在治疗计划过程中其负荷的动态变化是否可以预测治疗的临床结果?(3)这些细胞的表型和生物学特征是否有任何变化来区分预后亚型(4)共培养时CEPCs对CTCs的影响以及相互作用的基本生物学(5)我们能否在体外扩增这些细胞以鉴定真正的“转移前体细胞”或“癌症干细胞”并确定作为潜在治疗靶点的血管生成和转移的生物标志物。
公共卫生相关性:对个体参与者可能没有直接的医疗益处。然而,通过这项研究计划,我希望更多地了解新的转移标志物。利用一种新的集成微流控技术,循环细胞在癌症发生和转移中的生物学意义将被研究。参与研究项目的风险是合理的,以可能提高参与者和未来癌症患者的诊断,预后和治疗能力。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Sunitha Nagrath其他文献
Sunitha Nagrath的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Sunitha Nagrath', 18)}}的其他基金
Label free microfluidic isolation, characterization and ex vivo expansion of CTCs
CTC 的无标记微流体分离、表征和离体扩增
- 批准号:
9310696 - 财政年份:2017
- 资助金额:
$ 15.95万 - 项目类别: