Engineering Commons^™

Examining The Effects Of Macrophage Populations On Cancerous Tumor Growth., Grace E. Mahlbacher

Electronic Theses and Dissertations

The most abundant immune cell types of the tumor microenvironment macrophages recruited there by tumor-eluted factors. The role of these immune cells in tumor progression, and the interplay between tumor and immune cells is an emerging field of research with potential for novel treatment strategies. Here, a TIE2 expressing macrophage (TEM) subtype is integrated into a virtual tumor model. Within the 2D microenvironment, the TEM will differentiate from an extravasated monocyte precursor, congregate around the abluminal side of the vasculature in response to a chemoattractant gradient, secrete cytokines which favor differentiation of a separate angiogenic macrophage subtype [1]. The effects …

Influence Of Fibroblasts On Metastatic Cancer Cell Drug Resistance In A 3d Microfluidic Cell Array, Elizabeth C. Benoy

Dissertations and Theses

Modeling an accurate depiction of the tumor microenvironment, (TME), is essential to observe the effect external factors might have on the tumor in vivo. In cancer therapy specifically, the outcomes of clinical treatments are heavily dependent on drug testing methods despite the cytotoxic effects these methods might have on the patient. Our lab has previously developed a three layered microfluidic cell array (3D μFCA) to reconstruct the relevantly spatial configuration of tumor and microvasculature found in vivo in order to develop a more efficient tool of high throughput drug discovery and screening. In this study, we optimized this device to …

Bioengineered Platforms To Study Carcinoma Cell Response To Drug Treatment, Thuy V. Nguyen

Doctoral Dissertations

The tumor extracellular matrix (ECM) plays an important role in facilitating tumor growth and mediating tumor cells' resistance to drugs. However, during drug development, potential chemotherapeutics are screened in plastic plates, which lack relevant ECM physicochemical cues. In order to improve drug development process, this dissertation includes the development of relevant 2D and 3D biomaterial systems that can be used to study carcinoma cell response to drug treatment. A novel poly(ethylene glycol)-phosphorylcholine (PEG-PC) high-throughput biomaterial platform was developed to study how the ECM mechanochemical properties affect cancer cells' response to drug. The PEG-PC biomaterial is optically transparent, has a mechanical …

A Novel Minimally Invasive Tumour Localization Device, Doran Avivi

Electronic Thesis and Dissertation Repository

Lung cancer is one of the leading causes of death, by cancer. The usual treatment is surgical resection of tumours. However, patients who are weak or have poor pulmonary function are deemed unfit for surgery. For these patients, a minimally-invasive approach is desired. A major problem associated with minimally-invasive approaches is tumour localization in real time and accurate measurement of tool--tissue forces.

This thesis describes the design, analysis, manufacturing and validation of a minimally-invasive instrument for tumour localization, named Palpatron. The instrument has an end effector that is able to support two previously designed jaws, one containing an ultrasound sensor …

A Trans-Dimensional View Of Drug Resistance Evolution In Multiple Myeloma Patients, Timothy Jacobson

USF Tampa Graduate Theses and Dissertations

Multiple Myeloma (MM) is a treatable, yet incurable, malignancy of bone marrowplasma cells. This cancer affects many patients and many succumb to relapse of tumor burden despite a large number of available chemotherapeutic agents developed for therapy. This is because MM tumors are heterogeneous and receive protection from therapeutic agents by the microenvironment and other mechanisms including homologous MM-MM aggregation. Therefore, therapy failure and frequent patient relapse is due to the evolution of drug resistance, not a lack of available drugs. To analyze and understand this problem, the evolution of drug resistance has been explored and presented herein. We seek …

Enhancement Of Cancer Vaccine Efficacy Via Nanoparticle Or Molecular-Based Adjuvants, Myunggi An

Wayne State University Theses

Adjuvants are immunomodulators which enhance immune responses to vaccines. However, parenteral administration of unformulated adjuvants fails to reach lymph nodes (LNs), the anatomic organ where the primary functions of immune cells are orchestrated. The LN-targeting delivery plays the key roles in promoting immune activation and has the great potential to transform disease treatment. The main goal of this thesis is to develop efficient vaccine delivery systems to target therapeutics into draining lymph nodes (dLNs) for ensuring their immunostimulatory activity. We introduced therapeutic applications of activating TLR9 with synthetic CpG oligodeoxynucleotide (ODN) agonists in nanoparticle or molecular form to activate immune …

Decitabine-Loaded Nanogel Treatment To Reverse Cancer Drug Resistance, Samantha A. Cramer

ETD Archive

Cancers in which epigenetic changes, such as hypermethylation of DNA, lead to drug resistance cause the cancer to become unresponsive to existing chemotherapeutic treatments. The epigenetic drug – 5-aza-2’-deoxycytidine (decitabine, DAC) – is a potent hypomethylating agent, but its effect is transient due to its instability. Previous studies have shown that loading DAC into nanogel significantly enhances its antiproliferative effect (compared to DAC in solution) in drug-resistant breast cancer cells (MCF-7/ADR). Further, the previous studies demonstrated changes in the membrane lipid profile of resistant cells following treatment with DAC either as solution or in nanogels. The objective of the present …

Surface-Initiated Polymerizations For The Rapid Sorting Of Rare Cancer Cells, Jacob L. Lilly

Theses and Dissertations--Chemical and Materials Engineering

Cancer metastasis directly accounts for an estimated 90% of all cancer related deaths and is correlated with the presence of malignant cells in systemic circulation. This observed relationship has prompted efforts to develop a fluid biopsy, with the goal of detecting these rare cells in patient peripheral blood as surrogate markers for metastatic disease as a partial replacement or supplement to tissue biopsies. Numerous platforms have been designed, yet these have generally failed to support a reliable fluid biopsy due to poor performance parameters such as low throughput, low purity of enriched antigen positive cells, and insufficiently low detection thresholds …

Restriction And Characterization Of Human Breast Cancer Using A Three-Dimensional Embryonic Stem Cell Model, Bridget Mooney

Legacy Theses & Dissertations (2009 - 2024)

Human breast cancer is currently the highest diagnosed form of cancer and the second leading cause of cancer-related deaths in American women. Triple negative breast cancer is of the basal subtype and displays the worst prognosis owing to its highly metastatic properties. Current treatments focused on eradicating breast tumors in lieu of or following local therapy include chemotherapy, hormonal therapy, and targeted therapy. Hormonal therapy is not an option for triple negative breast cancer as it does not contain hormone receptors and there are currently no approved biological targeted therapies. Chemotherapy has proven unsuccessful because triple negative breast cancer is …

Creation Of A 3d Construct To Aid Cell Migration And Promote Cell Capture, Joseph Michael Sanders

Legacy Theses & Dissertations (2009 - 2024)

Most cancer-related deaths are attributed to metastasis. The tumor microenvironment is a complex environment which is not fully understood. The Nano Intravital Device (NANIVID) is a versatile, biocompatible device that allows for the manipulation of the tumor microenvironment in vitro and in vivo, providing a platform to study various aspects of tumor progression. The purpose of this study is to modify the NANIVID to resemble the tumor microenvironment in order to allow for a seamless transition from the in vivo environment into the engineered environment within the NANIVID. This engineered microenvironment will promote cell migration and cell capture. It has …

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 …

A Novel Biomaterial Enables Chemotactic Study Of Motile Central Nervous System-Derived Tumor Cells, Tanya Singh

Dissertations and Theses

"The local cell microenvironment plays an important role in maintaining the dynamics of the extracellular matrix (ECM) and the cell-ECM relationship. ECM is a complex network of macromolecules with distinct mechanical and biochemical characteristics [1]. The multifaceted interactions that occur between cells and the ECM are crucial to the regulation of processes that maintain homeostasis. These mechanisms are often deregulated during cancer onset and progression, which cause the ECM to become highly disorganized, alter the cell-matrix interactions, and promote increased hypervascularity and metastasis as these components are indicative of cancer progression. Medulloblastoma (MB) is one of the most common, malignant …

Impedance Sensing Of N2a And Astrocytes As Grounds For A Central Nervous System Cancer Diagnostic Device, Fraser Traves Smith Grove

Master's Theses

This thesis utilizes previously described manufacturing and design techniques for the creation of a PDMS-glass bonded microfluidic device, capable of electrochemical impedance spectroscopy (EIS). EIS has been used across various fields of research for different diagnostic needs. The major aim of this thesis was to capture cancerous and non-cancerous cells between micron sized electrodes within a microfluidic path, and to complete analysis on the measured impedances recorded from the two differing cell types. Two distinct ranges of impedance frequency were analyzed – the α dispersion range, which quantifies the impedance of the membranes of the cells of interest, and the …

Quantitative, Spatial Imaging Based Measurements To Assess Cellular Health And Oxygenation In A Tissue Engineered Test System, Erik Bland

All Dissertations

Three-dimensional in vitro tissue test systems are employed to examine cell behavior, test responses to drugs and vaccines, and answer basic biological questions. These systems are more physiologically relevant than two-dimensional cell cultures, and are more relevant, easier and less expensive to maintain than animal models. However, methods used to measure cell behavior and viability have been developed specifically for two-dimensional cell cultures or animal models, and are often not optimally translated to three-dimensional in vitro test systems. The purpose of this work was to aid in the development of three-dimensional, spatially controlled in vitro test systems, and to develop …

Impedance-Based Detection Of Tissue Using A Multi-Electrode Device, Shane Killian Fleshman

Master's Theses

Melanoma skin cancer is the abnormal growth of the melanocytes – the pigmented cells located in the epidermis. The current gold standard diagnostic technique for determining whether a lesion is cancerous involves subjectively examining suspicious lesions and performing an invasive biopsy to confirm melanoma. This method may neglect some lesions or cause scarring from biopsies that turn out to be benign. Thus, impedance-based detection using a multi-electrode device was investigated as a noninvasive technique to diagnose melanoma skin cancer. The multi-electrode device was designed with 8 equally spaced Ag/AgCl electrodes surrounding one central electrode at a 5 mm radius. The …

Quantification Of Vascular Parametric Indices Using Dynamic Contrast-Enhanced Magnetic Resonance Imaging, Areen Khaled Al.Bashir

Wayne State University Dissertations

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a non-invasive method used to evaluate the biological activity in early clinical trials of novel drugs targeting the tumor vasculature using gadolinium-DTPA (Gd) as a contrast agent. However, it has some limitations, such as reproducibility, data acquisition times, the presence of noise, extracting contrast concentration, estimating T1 relaxation and estimating pharmacokinetic parameters.

In this work, a new approach to used fixed T1(0) which provides more reproducible DCE results has been introduced. Using this new algorithm to quantify the vascular changes in DCE-MRI, a pre-clinical renal cell carcinoma (RCC) tumor model was used to …

Nanivid : A New Research Tool For Tissue Microenvironment Studies, Waseem Khan Raja

Legacy Theses & Dissertations (2009 - 2024)

Metastatic tumors are heterogeneous in nature and composed of subpopulations of cells having various metastatic potentials. The time progression of a tumor creates a unique microenvironment to improve the invasion capabilities and survivability of cancer cells in different microenvironments. In the early stages of intravasation, cancer cells establish communication with other cell types through a paracrine loop and covers long distances by sensing growth factor gradients through extracellular matrices. Cellular migration both in vitro and in vivo is a complex process and to understand their motility in depth, sophisticated techniques are required to document and record events in real time. …

Understanding The Molecular Dynamics Of Ypel3 And Fhit Gene Expression, Kevin Daniel Kelley

Browse all Theses and Dissertations

A comprehensive understanding of the molecular signaling pathways that regulate cell growth and proliferation is essential in the realization of new therapeutic options to facilitate early detection and eradication of malignancy. Understanding the transcriptional regulation of the YPEL3 and FHIT genes forms the basis of this dissertation. YPEL3, or Yippee-like 3, is a newly identified p53 target gene that inhibits tumor cell growth and is thus itself, a novel tumor suppressor gene. FHIT, or Fragile histidine triad, is a well known tumor suppressor gene and is regulated at the transcriptional level by another growth inhibitory protein, FOXO3a, a Forkhead box …

Inducing A Normal Phenotype In Breast Epithelial Cells Using A Three-Dimensional Basement Membrane Extract Culture System: A Study On The Reversion Of Cancer, Ross H. Booth

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Experimentally, traditional developmental models and transgenic animals consistently underscore the importance of studying cell behavior in the correct tissue context. However, live animal experimentation is inherently complex, and systematic assessment of the effects of individual variables, such as cell shape and matrix compliance on cell behavior, is extremely difficult at best. Two-dimensional monolayer culture of key individual cell types has provided abundant, fundamental information on cell response, but cannot be used to show the normal phenotype of breast epithelial cells. Furthermore, their results often fail to translate into in vivo and clinical studies. It has been previously established that normal …

Bio-Signal Analysis In Fatigue And Cancer Related Fatigue;Weakening Of Corticomuscular Functional Coupling, Qi Yang

ETD Archive

Fatigue is a common experience that reduces productivity and increases chance of injury, and has been reported as one of most common symptoms with greatest impact on quality-of-life parameters in cancer patients. Neural mechanisms behind fatigue and cancer related fatigue (CRF) are not well known. Recent research has shown dissociation between changes in brain and muscle signals during voluntary muscle fatigue, which may suggest weakening of functional corticomuscular coupling (fCMC). However, this weakening of brain-muscle coupling has never been directly evaluated. More important information could be gained if fCMC is directly detected during fatigue because a voluntary muscle contraction depends …

Biochemical Characterization Of Htrf1 And Htep1, Two Proteins Involved In Telomere Maintenance, Kambiz Tahmaseb

Browse all Theses and Dissertations

Telomeres are the structures that protect the ends of linear chromosomes from fusion and degradation. The telomere consists of tandem repeated DNA sequences that can range from hundreds of bases to kilo-bases depending on the organism. As the cells of an organism replicate their DNA, these repeats are lost due to the end replication problem, where the ends of linear DNA cannot be fully replicated. As the telomeres are shortened through each round of replication, they eventually reach a critical point. Once the telomeres are too short and the cell risks losing coding sequences, a signaling pathway is initiated that …