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The Microfluidic Intravital Window: A Tool for Manipulation and Imaging of the Tumor Microenvironment.

Record Type:	Electronic resources : Monograph/item
Title/Author:	The Microfluidic Intravital Window: A Tool for Manipulation and Imaging of the Tumor Microenvironment./
Author:	Butt, Logan.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2018,
Description:	138 p.
Notes:	Source: Dissertations Abstracts International, Volume: 80-06, Section: B.
Contained By:	Dissertations Abstracts International80-06B.
Subject:	Nanoscience. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10982647
ISBN:	9780438732568

The Microfluidic Intravital Window: A Tool for Manipulation and Imaging of the Tumor Microenvironment.
Butt, Logan.

The Microfluidic Intravital Window: A Tool for Manipulation and Imaging of the Tumor Microenvironment. - Ann Arbor : ProQuest Dissertations & Theses, 2018 - 138 p.

Source: Dissertations Abstracts International, Volume: 80-06, Section: B.

Thesis (Ph.D.)--State University of New York at Albany, 2018.

This item must not be added to any third party search indexes.

The tumor microenvironment (TME) is a heterogeneous collection of both healthy and pathological cells, whose complex interactions hold the key for understanding and overcoming cancer. Metastasis leverages these complex interactions into a sophisticated process by which single cells from the tumor disseminate into the blood and form new colonies in other organ systems. Subsequent formation of tumors throughout the body, as a direct result of metastatic events, is responsible for most deaths related to cancer, making metastasis a necessary target for cancer therapy. Metastasis requires invasion of a cancer cell towards the blood vessel, followed by penetration of the cell into the blood vessel. Not surprisingly, these processes involve multiple cell types working together. Namely, metastatic cancer cells have been shown to communicate in tandem with tumor-associated macrophages (TAMs) toward the endothelial cells of the blood vessel. This process, in breast cancer, involves a "paracrine loop," in which cancer cells secrete a known chemoattractant for TAMs, colony stimulating factor 1 (CSF-1), while TAMs secrete a chemoattractant for cancer cells, epidermal growth factor (EGF). Furthermore, the endothelial cells secrete the chemoattractant hepatocyte growth factor (HGF), which guides the cancer cell-TAM collective toward the blood vessel. At the blood vessel, a three-cell complex is formed, known as the Tumor Microenvironment of Metastasis (TMEM). The TMEM consists of a single metastatic cancer cell, a TAM, and one endothelial cell. TMEMs are highly stable and can persist for weeks. Through a complex signaling pathway, the TMEM forms an invadopod which is responsible for temporarily opening the blood vessel, allowing for other invasive cells and macrophages to stream in. By analyzing this pathway, researchers have developed a drug, Rebastinib, which inhibits metastasis and is currently showing promise in clinical trials. This is essentially important, as chemotherapy causes a large immune response which increases the number of TAMs and expediates TMEM formation. New tools are required to study the TME without losing context of those complex interactions. Such tools must be able to simultaneously image and manipulate the TME, so that the fate of individual cells can be observed in a variety of conditions. Furthermore, a tool is required to collect metastatic cells to run gene expression analysis and to unlock the secrets of metastasis. Proposed is a technology capable of accomplishing all of these tasks simultaneously by combining drug-release capabilities of the Nano Intravital Device (NANIVID), the imaging capabilities of the intravital window, and novel light-controlled microfluidic capabilities of azobenzene liquid crystal polymers (LCPs). The NANIVID has been previously developed and characterized as an implantable tool for the study of the TME by three functions: imaging, release, and collection. Of these, the most important and unique function is that of chemotaxis-based collection in solid tissue. NANIVIDs were analyzed according to device geometries and validated for collection in vitro and ex ovo . NANIVID capabilities were combined with intravital windows to form the microfluidic intravital window (MFIW), which is capable of all the functions of the NANIVID, along with the extremely stable and long timeframe of the intravital window. MFIWs have been fabricated and assembled using PDMS, glass, and plexiglass. Early studies have shown that the MFIWs can release factors into solid tissue, image with subcellular resolution in vivo, and achieve collection using custom-fabricated microneedles. Finally, for complete control over MFIW function, a new technology has been created which combines microfabrication techniques with liquid crystal polymerization techniques to generate custom azobenzene LCPs at any 2D configuration. These azobenzene LCPs exhibit macroscopic bending when irradiated with certain wavelengths and polarizations of light, and are capable of converting light energy into mechanical energy. New azobenzene LCP geometries were created for the first time and implemented into PDMS membranes for microfluidic capabilities and for integration with the MFIW.

ISBN: 9780438732568Subjects--Topical Terms:

587832
Nanoscience.
Subjects--Index Terms:

Cancer metastasis

The Microfluidic Intravital Window: A Tool for Manipulation and Imaging of the Tumor Microenvironment.
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520 $a The tumor microenvironment (TME) is a heterogeneous collection of both healthy and pathological cells, whose complex interactions hold the key for understanding and overcoming cancer. Metastasis leverages these complex interactions into a sophisticated process by which single cells from the tumor disseminate into the blood and form new colonies in other organ systems. Subsequent formation of tumors throughout the body, as a direct result of metastatic events, is responsible for most deaths related to cancer, making metastasis a necessary target for cancer therapy. Metastasis requires invasion of a cancer cell towards the blood vessel, followed by penetration of the cell into the blood vessel. Not surprisingly, these processes involve multiple cell types working together. Namely, metastatic cancer cells have been shown to communicate in tandem with tumor-associated macrophages (TAMs) toward the endothelial cells of the blood vessel. This process, in breast cancer, involves a "paracrine loop," in which cancer cells secrete a known chemoattractant for TAMs, colony stimulating factor 1 (CSF-1), while TAMs secrete a chemoattractant for cancer cells, epidermal growth factor (EGF). Furthermore, the endothelial cells secrete the chemoattractant hepatocyte growth factor (HGF), which guides the cancer cell-TAM collective toward the blood vessel. At the blood vessel, a three-cell complex is formed, known as the Tumor Microenvironment of Metastasis (TMEM). The TMEM consists of a single metastatic cancer cell, a TAM, and one endothelial cell. TMEMs are highly stable and can persist for weeks. Through a complex signaling pathway, the TMEM forms an invadopod which is responsible for temporarily opening the blood vessel, allowing for other invasive cells and macrophages to stream in. By analyzing this pathway, researchers have developed a drug, Rebastinib, which inhibits metastasis and is currently showing promise in clinical trials. This is essentially important, as chemotherapy causes a large immune response which increases the number of TAMs and expediates TMEM formation. New tools are required to study the TME without losing context of those complex interactions. Such tools must be able to simultaneously image and manipulate the TME, so that the fate of individual cells can be observed in a variety of conditions. Furthermore, a tool is required to collect metastatic cells to run gene expression analysis and to unlock the secrets of metastasis. Proposed is a technology capable of accomplishing all of these tasks simultaneously by combining drug-release capabilities of the Nano Intravital Device (NANIVID), the imaging capabilities of the intravital window, and novel light-controlled microfluidic capabilities of azobenzene liquid crystal polymers (LCPs). The NANIVID has been previously developed and characterized as an implantable tool for the study of the TME by three functions: imaging, release, and collection. Of these, the most important and unique function is that of chemotaxis-based collection in solid tissue. NANIVIDs were analyzed according to device geometries and validated for collection in vitro and ex ovo . NANIVID capabilities were combined with intravital windows to form the microfluidic intravital window (MFIW), which is capable of all the functions of the NANIVID, along with the extremely stable and long timeframe of the intravital window. MFIWs have been fabricated and assembled using PDMS, glass, and plexiglass. Early studies have shown that the MFIWs can release factors into solid tissue, image with subcellular resolution in vivo, and achieve collection using custom-fabricated microneedles. Finally, for complete control over MFIW function, a new technology has been created which combines microfabrication techniques with liquid crystal polymerization techniques to generate custom azobenzene LCPs at any 2D configuration. These azobenzene LCPs exhibit macroscopic bending when irradiated with certain wavelengths and polarizations of light, and are capable of converting light energy into mechanical energy. New azobenzene LCP geometries were created for the first time and implemented into PDMS membranes for microfluidic capabilities and for integration with the MFIW.
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