Enabling NF-kB Signal Transduction Studies in Primary Multiple Myeloma Cells

在原发性多发性骨髓瘤细胞中进行 NF-kB 信号转导研究

基本信息

  • 批准号:
    8239386
  • 负责人:
  • 金额:
    $ 28.11万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2012
  • 资助国家:
    美国
  • 起止时间:
    2012-06-21 至 2017-04-30
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): In contrast to highly sensitive genomic and proteomic methods that primarily evaluate the state of cancer specimens, functional analyses of primary patient samples to assess their biological responses to various experimental conditions are difficult because of the often limited number of live primary cells that can be obtained from patient biopsy samples. Thus, overcoming this technical barrier has the potential to transform our ability to significantly increase translational cancer research approaches. By combining expertise in, cancer cell signaling, bioengineering, and primary patient care, the Miyamoto-Beebe-Callander team proposes to improve our ability to functionally analyze NF-kB signal transduction responses in primary patient multiple myeloma (MM) samples. Specifically, we propose to develop innovative microchannel culture devices and implement functional studies to investigate a dogma-challenging NF-kB-survival pathway in MM. We have already developed prototype culture devices that increase our ability to analyze primary MM cells. These microculture systems also provide the flexibility to study components of the tumor microenvironment, such as tumor-supporting bone marrow stromal cells (BMSCs). Under Aim 1 we will dissect drug resistance-inducing NF-kB signaling mechanisms in primary MM cells using the first generation microscale cell culture chambers (MCCCs). We also aim to reveal patient individualized information by co- culturing MM cells and BMSCs derived from the same patients, a paradigm shift from the conventional experimental setup where patient sources of MM and BMSCs are randomly mixed. Under Aim 2 we will further improve functional micro-scale assays with additional functionalities and with even smaller cell numbers per condition, thus greatly expanding the scope of translational research in MM. The micro-culture technology proposed has the potential to rapidly change the methods used for investigating signal transduction studies, including NF-kB, in MM and other blood and possibly solid cancer types. PUBLIC HEALTH RELEVANCE: Many anticancer agents are used to kill cancer cells, but unfortunately cancer cells turn on survival mechanisms to counter the death effect. One of these mechanisms is the activation of the transcription factor NF-kB that rapidly turns on synthesis of survival genes. The proposed research will reveal an important mechanism of NF-kB pathway in patient multiple myeloma cells by developing innovative microculture methods that enable the systematic and high throughput analysis of precious patient cancer samples. This study is expected to uncover an important survival mechanism that may serve as a future drug target to improve treatment of this currently incurable cancer type.
描述(由申请人提供):与主要评价癌症样本状态的高灵敏度基因组和蛋白质组学方法相比,由于可从患者活检样本中获得的活原代细胞数量通常有限,因此难以对原代患者样本进行功能分析以评估其对各种实验条件的生物学反应。因此,克服这一技术障碍有可能改变我们的能力,显着增加转化癌症研究方法。Miyamoto-Beebe-卡兰德团队结合了癌细胞信号传导、生物工程和初级患者护理方面的专业知识,提出提高我们在原发性多发性骨髓瘤(MM)患者样本中功能性分析NF-κ B信号转导反应的能力。具体而言,我们建议开发创新的微通道培养装置,并实施功能研究,以调查MM中具有教条挑战性的NF-κ B存活途径。我们已经开发出原型培养装置,提高了我们分析原代MM细胞的能力。这些微培养系统还提供了研究肿瘤微环境组分的灵活性,例如肿瘤支持骨髓基质细胞(BMSC)。在目标1下,我们将使用第一代微型细胞培养室(MCCC)剖析原代MM细胞中诱导耐药的NF-kB信号传导机制。我们还旨在通过共培养来自相同患者的MM细胞和BMSC来揭示患者个体化信息,这是从常规实验设置的范式转变,其中MM和BMSC的患者来源被随机混合。在目标2下,我们将进一步改进功能性微量测定,增加额外的功能,每种条件下的细胞数量甚至更少,从而大大扩大MM转化研究的范围。提出的微培养技术有可能迅速改变用于研究信号转导研究的方法,包括MM和其他血液和可能的实体癌类型中的NF-κ B。 公共卫生关系: 许多抗癌药物被用来杀死癌细胞,但不幸的是,癌细胞会开启生存机制来对抗死亡效应。这些机制之一是转录因子NF-κ B的激活,其快速开启存活基因的合成。拟议的研究将揭示患者多发性骨髓瘤细胞中NF-kB通路的重要机制,通过开发创新的微培养方法,使宝贵的患者癌症样本的系统和高通量分析成为可能。这项研究有望揭示一种重要的生存机制,可能作为未来的药物靶点,以改善这种目前无法治愈的癌症类型的治疗。

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(1)

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David J Beebe其他文献

Molecular analysis of antigen presentation machinery in circulating tumor cells from renal cell carcinoma and prostate cancer
  • DOI:
    10.1186/2051-1426-1-s1-p57
  • 发表时间:
    2013-11-01
  • 期刊:
  • 影响因子:
    10.600
  • 作者:
    Joshua M Lang;Jacob T Tokar;Jamie Sperger;Benjamin P Casavant;Scott M Berry;Lindsay N Strotman;David J Beebe
  • 通讯作者:
    David J Beebe

David J Beebe的其他文献

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{{ truncateString('David J Beebe', 18)}}的其他基金

Development of a human intestinal microphysiological system for the study of immune responses to protozoan parasites
开发人体肠道微生理系统用于研究原生动物寄生虫的免疫反应
  • 批准号:
    10733303
  • 财政年份:
    2023
  • 资助金额:
    $ 28.11万
  • 项目类别:
Under-oil open microfluidic system (UOMS) for studying systemic fungal infection
用于研究全身真菌感染的油下开放式微流体系统 (UOMS)
  • 批准号:
    10333399
  • 财政年份:
    2021
  • 资助金额:
    $ 28.11万
  • 项目类别:
Under-oil open microfluidic system (UOMS) for studying systemic fungal infection
用于研究全身真菌感染的油下开放式微流体系统 (UOMS)
  • 批准号:
    10552700
  • 财政年份:
    2021
  • 资助金额:
    $ 28.11万
  • 项目类别:
Under-oil open microfluidic system (UOMS) for studying systemic fungal infection
用于研究全身真菌感染的油下开放式微流体系统 (UOMS)
  • 批准号:
    10209529
  • 财政年份:
    2021
  • 资助金额:
    $ 28.11万
  • 项目类别:
Enhancing Epigenetic Analysis Of Rare Cells With Multi-Phase Microfluidics
利用多相微流体增强稀有细胞的表观遗传分析
  • 批准号:
    9916997
  • 财政年份:
    2020
  • 资助金额:
    $ 28.11万
  • 项目类别:
Enhancing Epigenetic Analysis Of Rare Cells With Multi-Phase Microfluidics
利用多相微流体增强稀有细胞的表观遗传分析
  • 批准号:
    10331769
  • 财政年份:
    2020
  • 资助金额:
    $ 28.11万
  • 项目类别:
Mechanisms of microenvironment mediated resistance to cancer cell surface targeted therapeutics
微环境介导的癌细胞表面靶向治疗耐药机制
  • 批准号:
    10686449
  • 财政年份:
    2020
  • 资助金额:
    $ 28.11万
  • 项目类别:
Enhancing Epigenetic Analysis Of Rare Cells With Multi-Phase Microfluidics
利用多相微流体增强稀有细胞的表观遗传分析
  • 批准号:
    10094211
  • 财政年份:
    2020
  • 资助金额:
    $ 28.11万
  • 项目类别:
Mechanisms of microenvironment mediated resistance to cancer cell surface targeted therapeutics
微环境介导的癌细胞表面靶向治疗耐药机制
  • 批准号:
    10263962
  • 财政年份:
    2020
  • 资助金额:
    $ 28.11万
  • 项目类别:
A multiplexed micro scale assay for real time analysis of pediatric immune cell function
用于实时分析儿科免疫细胞功能的多重微量测定
  • 批准号:
    10380807
  • 财政年份:
    2020
  • 资助金额:
    $ 28.11万
  • 项目类别:

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