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A Three-Dimensional-Engineered Matrix To Study The Microenvironment Of Cancer Stem Cells, Samaneh Kamali Sarvestani Dec 2014

A Three-Dimensional-Engineered Matrix To Study The Microenvironment Of Cancer Stem Cells, Samaneh Kamali Sarvestani

Theses and Dissertations

Maintenance of cancer stem cells (CSCs) is regulated by their microenvironment. As cancer cells are affected by many factors in their microenvironment, a major challenge is to isolate the effect of a specific factor on CSCs while keeping other factors unchanged. We developed a synthetic inert 3D Poly Ethylene Glycol Di-Acrylate (PEGDA) gel culture system as a unique tool to study the effect of microenvironmental factors on CSCs response. Synthetic hydrogels provide the flexibility to design three-dimensional (3D) matrices to isolate and study individual factors in the tumor microenvironment. The first objective of this work was to investigate the effect …


A Four-Dimensional Image Reconstruction Framework For Pet Under Arbitrary Geometries, Aswin John Mathews Dec 2014

A Four-Dimensional Image Reconstruction Framework For Pet Under Arbitrary Geometries, Aswin John Mathews

McKelvey School of Engineering Theses & Dissertations

Positron Emission Tomography (PET) is a functional imaging modality with applications ranging from the treatment of cancer, studying neurological diseases and disease models. Virtual-Pinhole PET technology improves the image quality in terms of resolution and contrast recovery. The technology calls for having a detector with smaller crystals placed near a region of interest in a conventional whole-body PET scanner. The improvement is from the higher spatial sampling of the imaging area near the detector. A prototype half-ring PET insert built to study head-and-neck cancer imaging was extended to breast cancer imaging. We have built a prototype half-ring PET insert for …


Effect Of Chemotherapeutic Treatment Schedule On A Tissue Transport Model, Dan E. Ganz Nov 2014

Effect Of Chemotherapeutic Treatment Schedule On A Tissue Transport Model, Dan E. Ganz

Masters Theses

Current chemotherapeutic treatment schedule prediction methods rely heavily on PK/PD-based models and overlook the important contribution of tissue-level transport and binding. Tissue-level transport and binding phenomena are essential to understanding drug delivery and efficacy in tumors. Drugs with desirable PK/PD properties often fail in vivo due to poor tissue-level transport. We developed an in silico method to predict the effect of treatment schedule on efficacy that couples PK/PD with tissue-level transport. Treatment schedules were implemented on theoretical drugs with different PK/PD and transport properties. For each drug with a given clearance rate, diffusivity, and binding, treatment schedules consisting of one …


Design Of A Targeted Bacterial Drug Delivery Vector For The Treatment Of Cancer And Metastases, Charles Alexander Swofford Aug 2014

Design Of A Targeted Bacterial Drug Delivery Vector For The Treatment Of Cancer And Metastases, Charles Alexander Swofford

Doctoral Dissertations

Engineered Salmonella possess unique capabilities that make them ideal drug delivery vectors for tumors. Targeted bacterial delivery of anticancer proteins has the ability to overcome therapeutic resistance in tumors that limits the efficacy of chemotherapeutics. In my doctoral research, I identified a protein-drug that can be expressed by bacteria and rapidly kills cancer cells. I also created a density dependent switch that initiates gene expression in tumors and prevents expression in healthy tissue. Combining these two systems has created a potent anti-cancer system that targets tumors with minimal toxicity. I cloned genes for five potential anti-cancer proteins into Salmonella. …


Expanding Applications Of The Nano Intravital Device As A Platform For Exploring Tumor Microenvironments, Michael Padgen Jan 2014

Expanding Applications Of The Nano Intravital Device As A Platform For Exploring Tumor Microenvironments, Michael Padgen

Legacy Theses & Dissertations (2009 - 2024)

The tumor microenvironment has been demonstrated to be a key determinant in the progression of cancer. Unfortunately, the mechanisms behind the different microenvironments (cytokine gradients, hypoxia, hypoglycemia, etc) have not been fully elucidated. Identifying these mechanisms can lead to targeted, individualized therapy to prevent metastasis. The Nano Intravital Device (NANIVID) is a microfabricated, implantable device designed to initiate specific microenvironments in vivo so that the time course of the effects can be observed. With both spatial and temporal control over the induced environments, the affected regions of the tumor can be compared to the rest of the tumor. The NANIVID …


An Implantable Device For Manipulation Of The In Vivo Tumor Microenvironment, James K. Williams Jan 2014

An Implantable Device For Manipulation Of The In Vivo Tumor Microenvironment, James K. Williams

Legacy Theses & Dissertations (2009 - 2024)

In the past decade, it has become increasingly recognized that interactions between cancer cells and the tumor microenvironment (TME) regulate metastasis. One such interaction is the paracrine loop between macrophages and cancer cells which drives metastatic invasion in mammary tumors. Tumor associated macrophages release epidermal growth factor (EGF), a chemoattractant which induces the migration of cancer cells toward the blood vessels. The cancer cells reciprocate by releasing a macrophage chemoattractant, colony-stimulating factor 1 (CSF-1), resulting in the co-migration of both cell types and subsequent intravasation. In this work, a new technology has been developed for studying the mechanisms by which …