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Microfluidic Biopsy Trapping Device ...
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Holton, Angela.
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Microfluidic Biopsy Trapping Device for the Real-time Monitoring of the Tumor Microenvironment.
紀錄類型:
書目-電子資源 : Monograph/item
正題名/作者:
Microfluidic Biopsy Trapping Device for the Real-time Monitoring of the Tumor Microenvironment./
作者:
Holton, Angela.
出版者:
Ann Arbor : ProQuest Dissertations & Theses, : 2017,
面頁冊數:
220 p.
附註:
Source: Dissertations Abstracts International, Volume: 79-06, Section: B.
Contained By:
Dissertations Abstracts International79-06B.
標題:
Molecular biology. -
電子資源:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10637826
ISBN:
9780355521801
Microfluidic Biopsy Trapping Device for the Real-time Monitoring of the Tumor Microenvironment.
Holton, Angela.
Microfluidic Biopsy Trapping Device for the Real-time Monitoring of the Tumor Microenvironment.
- Ann Arbor : ProQuest Dissertations & Theses, 2017 - 220 p.
Source: Dissertations Abstracts International, Volume: 79-06, Section: B.
Thesis (Ph.D.)--University of South Florida, 2017.
This item must not be sold to any third party vendors.
The tumor microenvironment is composed of cellular and stromal components such as tumor cells, mesenchymal cells, immune cells, cancer associated fibroblasts and the supporting extracellular matrix. The tumor microenvironment provides crucial support for growth and progression of tumor cells and affects tumor response to therapeutic interventions. To better understand tumor biology and to develop effective cancer therapeutic agents it is important to develop preclinical platforms that can faithfully recapitulate the tumor microenvironment and the complex interaction between the tumor and its surrounding stromal elements. Drug studies performed in vitro with conventional two-dimensional cancer cell line models do not optimally represent clinical drug response as they lack true tumor heterogeneity and are often performed in static culture conditions lacking stromal tumor components that significantly influence the metabolic activity and proliferation of cells. Recent microfluidic approaches aim to overcome such obstacles with the use of cell lines derived in artificial three-dimensional supportive gels or micro-chambers. However, absence of a true tumor microenvironment and full interstitial flow, leads to less than optimal evaluation of tumor response to drug treatment. Here we report a continuous perfusion microfluidic device coupled with microscopy and image analysis for the assessment of drug effects on intact fresh tumor tissue. We have demonstrated that fine needle aspirate biopsies obtained from patient-derived xenograft models of adenocarcinoma of the lung can successfully be analyzed for their response to ex vivo drug treatment within this biopsy trapping microfluidic device, wherein a protein kinase C inhibitor, staurosporine, was used to assess tumor cell death as a proof of principle. Lastly, we tested the model for its ability to demonstrate similar results found in clinic when using a Wee1 inhibitor on osteosarcoma and an epidermal growth factor receptor inhibitor, Erlotinib, and inhibitors of programmed death 1 receptor and programmed death ligand 1 on lung adenocarcinoma fine needle aspirate biopsies. This approach has the potential to study tumor tissue within its intact microenvironment to better understand tumor response to drug treatments and eventually to choose the most effective drug and drug combination for individual patients in a cost effective and timely manner.
ISBN: 9780355521801Subjects--Topical Terms:
517296
Molecular biology.
Microfluidic Biopsy Trapping Device for the Real-time Monitoring of the Tumor Microenvironment.
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The tumor microenvironment is composed of cellular and stromal components such as tumor cells, mesenchymal cells, immune cells, cancer associated fibroblasts and the supporting extracellular matrix. The tumor microenvironment provides crucial support for growth and progression of tumor cells and affects tumor response to therapeutic interventions. To better understand tumor biology and to develop effective cancer therapeutic agents it is important to develop preclinical platforms that can faithfully recapitulate the tumor microenvironment and the complex interaction between the tumor and its surrounding stromal elements. Drug studies performed in vitro with conventional two-dimensional cancer cell line models do not optimally represent clinical drug response as they lack true tumor heterogeneity and are often performed in static culture conditions lacking stromal tumor components that significantly influence the metabolic activity and proliferation of cells. Recent microfluidic approaches aim to overcome such obstacles with the use of cell lines derived in artificial three-dimensional supportive gels or micro-chambers. However, absence of a true tumor microenvironment and full interstitial flow, leads to less than optimal evaluation of tumor response to drug treatment. Here we report a continuous perfusion microfluidic device coupled with microscopy and image analysis for the assessment of drug effects on intact fresh tumor tissue. We have demonstrated that fine needle aspirate biopsies obtained from patient-derived xenograft models of adenocarcinoma of the lung can successfully be analyzed for their response to ex vivo drug treatment within this biopsy trapping microfluidic device, wherein a protein kinase C inhibitor, staurosporine, was used to assess tumor cell death as a proof of principle. Lastly, we tested the model for its ability to demonstrate similar results found in clinic when using a Wee1 inhibitor on osteosarcoma and an epidermal growth factor receptor inhibitor, Erlotinib, and inhibitors of programmed death 1 receptor and programmed death ligand 1 on lung adenocarcinoma fine needle aspirate biopsies. This approach has the potential to study tumor tissue within its intact microenvironment to better understand tumor response to drug treatments and eventually to choose the most effective drug and drug combination for individual patients in a cost effective and timely manner.
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