Human Tissue Culture Bioreactor and Hyperpolarized MR for Biomarker Discovery

用于生物标志物发现的人体组织培养生物反应器和超极化 MR

基本信息

  • 批准号:
    8670990
  • 负责人:
  • 金额:
    $ 24.9万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2013
  • 资助国家:
    美国
  • 起止时间:
    2013-07-01 至 2016-06-30
  • 项目状态:
    已结题

项目摘要

Project Summary Through this Pathway to Independence Award, I hope to acquire the skills necessary to obtain a faculty position with an independent research program focused on the bioengineering and implementation of novel 3D cell and tissue culture bioreactors, and the use this platform in conjunction with hyperpolarized (HP) 13C MR to better study cancer metabolism. Due to the biologic and pathologic complexity of prostate cancer, there is an urgent clinical need to develop more sensitive and specific imaging markers for improved prostate cancer patient-specific treatment planning and early assessment of therapeutic failure. An extraordinary new technique utilizing hyperpolarized (HP) metabolic substrates has the potential to provide these MR biomarkers. Recent HP MR studies in cell and animal models suggest that HP metabolic markers reflect enzymatic fluxes and may provide a more accurate measure of prostate cancer presence, progression and response to therapy. However, available murine and cell culture models don't reliably mimic human disease, thus we propose a novel combination of HP 13C MR and NMR-compatible 3D tissue culture bioreactors to study the real-time metabolism of living human prostate tissue slices (TSCs). The overall objective of this research are to engineer an NMR-compatible, 3D Tissue Culture Bioreactor for use with human TSCs and use it to identify HP molecular imaging markers for improved prostate cancer patient- specific treatment planning and early assessment of response to targeted therapy. Accomplishing these aims will require additional training in the areas of primary cell and tissue cultures, prostate biochemistry and pathology, HP probe development, micro-engineering, biotransport, and pharmacokinetics. Utilizing this new training, the first aim is to optimize conditions for maintaining human prostate TSCs in an NMR-compatible, 3D tissue culture bioreactor and to verify the metabolic integrity of TSCs over time. Continuous 31P will be used to monitor the progression of tissue slices in the bioreactor with time. Dynamic acquisitions of HP 13C MR will be used to calculate fluxes associated with metabolism of pyruvate and other probes in real time. This data will be compared to histopathology before and after culture in the bioreactor to assess changes. The second aim is to use this new experimental model to compare normal and malignant prostate tissues metabolism, and importantly, determine whether HP metabolites correlate with pathologic grade and their relationship to metabolism and biotransport. The third aim is to use this platform to identify HP markers of therapeutic response to PI3K/mTOR inhibitors. It is the goal of this proposal to develop an engineered system, which can overcome the limitations of current murine and cell cultures models and aid in the development of relevant biomarkers for translation to the clinic. While the focus of the research in this Pathway to Independence Award is on prostate cancer, the combination of NMR-compatible primary tissue culture bioreactor platform combined with high sensitivity HP MR probes would have wide applicability across a variety of diseases and imaging modalities.
项目总结

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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Kayvan R Keshari其他文献

Kayvan R Keshari的其他文献

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{{ truncateString('Kayvan R Keshari', 18)}}的其他基金

Interrogation of the oxidative-stress-induced leukemia program in vivo using metabolic imaging
使用代谢成像研究体内氧化应激诱导的白血病程序
  • 批准号:
    10729140
  • 财政年份:
    2023
  • 资助金额:
    $ 24.9万
  • 项目类别:
Image-guided Trp-IDO/TDO-Kyn-AHR pathway inhibition, combined with immunotherapy
图像引导 Trp-IDO/TDO-Kyn-AHR 通路抑制结合免疫治疗
  • 批准号:
    10600027
  • 财政年份:
    2021
  • 资助金额:
    $ 24.9万
  • 项目类别:
Image-guided Trp-IDO/TDO-Kyn-AHR pathway inhibition, combined with immunotherapy
图像引导 Trp-IDO/TDO-Kyn-AHR 通路抑制结合免疫治疗
  • 批准号:
    10721993
  • 财政年份:
    2021
  • 资助金额:
    $ 24.9万
  • 项目类别:
Leveraging fructose transport to create a privileged substrate to selectively fuel T cells
利用果糖运输创造一种特殊底物来选择性地为 T 细胞提供燃料
  • 批准号:
    10529307
  • 财政年份:
    2020
  • 资助金额:
    $ 24.9万
  • 项目类别:
Visualizing oxidative stress using hyperpolarized magnetic resonance
使用超极化磁共振可视化氧化应激
  • 批准号:
    10037873
  • 财政年份:
    2020
  • 资助金额:
    $ 24.9万
  • 项目类别:
Leveraging fructose transport to create a privileged substrate to selectively fuel T cells
利用果糖运输创造一种特殊底物来选择性地为 T 细胞提供燃料
  • 批准号:
    10318220
  • 财政年份:
    2020
  • 资助金额:
    $ 24.9万
  • 项目类别:
Visualizing oxidative stress using hyperpolarized magnetic resonance
使用超极化磁共振可视化氧化应激
  • 批准号:
    10402394
  • 财政年份:
    2020
  • 资助金额:
    $ 24.9万
  • 项目类别:
Visualizing oxidative stress using hyperpolarized magnetic resonance
使用超极化磁共振可视化氧化应激
  • 批准号:
    10162569
  • 财政年份:
    2020
  • 资助金额:
    $ 24.9万
  • 项目类别:
Visualizing oxidative stress using hyperpolarized magnetic resonance
使用超极化磁共振可视化氧化应激
  • 批准号:
    10612868
  • 财政年份:
    2020
  • 资助金额:
    $ 24.9万
  • 项目类别:
Human Tissue Culture Bioreactor and Hyperpolarized MR for Biomarker Discovery
用于生物标志物发现的人体组织培养生物反应器和超极化 MR
  • 批准号:
    8691806
  • 财政年份:
    2013
  • 资助金额:
    $ 24.9万
  • 项目类别:

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