Biomedical Engineering and Bioengineering Commons^™

Photodynamic Therapy To Treat Triple Negative Breast Cancer In Vitro, Hunter S. Warren

All Theses

Triple negative breast cancer (TNBC) is the most resilient form of breast cancer, being one of the leading causes of death for women and making up 7% of all cancer deaths. Photodynamic therapy (PDT) offers a minimally invasive solution to TNBC as a passive-targeting treatment that reduces the need for other well established yet harsh treatments that can be taxing on the patient. PDT involves the use of a high-energy red light on the area of a tumor injected with photosensitizers (PS) that generate reactive oxygen species (ROS) in the tumor, triggering cell death. The PS tetra(hydroxyphenyl)chlorin (m-THPC) was used …

Seeing The Big Picture: System Architecture Trends In Endoscopy And Led-Based Hyperspectral Subsystem Intergration, Craig M. Browning

<strong> Theses and Dissertations </strong>

Early-stage colorectal lesions remain difficult to detect. Early development of neoplasia tends to be small (less than 10 mm) and flat and difficult to distinguish from surrounding mucosa. Additionally, optical diagnosis of neoplasia as benign or malignant is problematic. Low rates of detection of these lesions allow for continued growth in the colorectum and increased risk of cancer formation. Therefore, it is crucial to detect neoplasia and other non-neoplastic lesions to determine risk and guide future treatment. Technology for detection needs to enhance contrast of subtle tissue differences in the colorectum and track multiple biomarkers simultaneously. This work implements one …

Extracellular Matrix Stiffness As A Cue To Shape Phenotypic Evolution Of Triple Negative Breast Cancer, Ning-Hsuan Tseng

Doctoral Dissertations

Accumulation of epigenetic and genetic changes results in oncogenic transformation of epithelial cells. During breast cancer metastasis, while the extracellular matrix (ECM) becomes stiffer, breast cancer cells transmit mechanical forces into intracellular tension and activate signaling pathways influencing growth, migration, and metastasis. Once cancer cells detach from the primary tumor, they intravasate into the vasculature, survive in the circulation, extravasate and adapt to a new microenvironment of a secondary site. Throughout the process, only a very small population of cancer cells survive, and they are likely to reside at the metastatic sites for several years. The most frequent metastatic sites …

Sequential Illumination In A Tomographic Microendoscopic Probe For Imaging Tumor Microvasculature, Zachariah Neumeier

Biomedical Engineering Undergraduate Honors Theses

Knowledge of colorectal cancer biology is improving how we approach cancer treatment. Specifically, the tumor microenvironment and abnormal angiogenesis are of particular interest. Optical methods are a prime candidate for research of the tumor microenvironment due to their ability to quantitively assess tissue structure and perfusion in real time. Particularly, the “transport scattering regime” has been identified as a method of obtaining high-resolution images and reflectance spectroscopy data; this light scattering regime has been demonstrated compatible with endoscopic imaging systems. In this study, a proof-of-concept optical imaging system is presented, capable of resolving absorbers within scattering turbid media using a …

The Effects Of Metronomic And Maximum-Tolerated Dose Chemotherapy In Colorectal Cancer Angiogenesis: A Combined Approach Using Endoscopic Diffuse Reflectance Spectroscopy And Mrna Expression, Ariel Isaac Mundo Ortiz

Graduate Theses and Dissertations

Colorectal cancer (CRC) continues to be one of the most incident and deadliest types of cancer worldwide. Chemotherapy has proven effective to reduce tumor burden for CRC patients, but there are several disadvantages associated with the use of mainstay maximtolerated dose (MTD) chemotherapeutic strategies. Metronomic chemotherapy (MET) has been developed as an alternative that addresses the shortcomings of maximum-tolerated dose chemotherapy but so far its effectiveness as a neoadjuvant strategy for CRC has not been explored.

This dissertation uses a combined optics and molecular biology approach (using diffuse reflectance spectroscopy and mRNA expression) to study the changes in angiogenesis and …

Investigating The Impact Of Hypoxia On Reactive Oxygen Species Generation Within Murine Breast Cancer Cells, Jared Mcpeake

Biomedical Engineering Undergraduate Honors Theses

When cancer metastasizes from a primary tumor site to secondary site through the bloodstream or lymph, the cancer becomes more difficult to treat. For this reason, it is vital to study what indicates the metastatic potential of a tumor. Current research has shown that cell lines with high metastatic potential display increased levels of metabolic adaptability over their nonmetastatic counterparts after undergoing hypoxic conditions. One method of assessing this adaptability is to measure the concentration of reactive oxygen species (ROS) produced by the cells while undergoing oxidative stress. In highly adaptable metastatic cells, an increase of ROS buildup within the …

Synthesis Of Thiol-Acrylate Hydrogels For 3d Cell Culture And Microfluidic Applications, Anowar Hossain Khan

LSU Doctoral Dissertations

Globally cell culture is an $18.98 billion industry as of 2020, with an 11.6 percent annual growth rate. Drug discovery has an estimated worth of $69.8 billion in 2020 and is predicted to grow to $110.4 billion by 2025. Three-dimensional (3D) cell culture of cancer cells is one of the rapidly growing felids since it better recapitulates in vivo conditions compared to two-dimensional (2D) models. However, it is challenging to grow 3D tumor spheroids outside the body, and some of the existing technology can generate these spheroids outside the human body but poorly mimic in vivo tumor models. Therefore, there …

Longitudinal Monitoring Of Tumor Response To Immune Checkpoint Inhibitors Using Diffuse Optical Spectroscopy, Joel Isaac Rodriguez Troncoso

Graduate Theses and Dissertations

Immune checkpoint drugs have completely changed the way people treat metastatic melanoma and non-small-cell lung cancer. While the impacts of these immunological checkpoints and their suppression on T cell function are well characterized, their consequences on the tumor microenvironment are not. In a CT26 mouse colorectal cancer model, we employed diffuse reflectance spectroscopy to track in vivo tumor microenvironmental alterations in response to immune checkpoint inhibitors. On three separate days, animals bearing CT26 tumor xenografts were given anti-PD-L1, anti-CTLA-4, a combination of both inhibitors, and isotype control. Within the first 6 days, monotherapy with either anti-PD-L1 or anti-CTLA-4 resulted in …

Experimental And Analysis Of Electromagnetic Characterization Of Biological And Non-Biological Materials In Microwave, Millimeter-Wave, And Terahertz Frequency Bands, Nagma Vohra

Graduate Theses and Dissertations

The goal of this research is to characterize the electromagnetic properties of biological and non-biological materials at terahertz (THz), millimeter-wave, and microwave frequency bands. The biological specimens are measured using the THz imaging and spectroscopy system, whereas the non-biological materials are measured using the microwave and millimeter-wave free-space system. These facilities are located in the Engineering Research Center at the University of Arkansas. The THz imaging system (TPS 3000) uses a Ti-Sapphire laser directed on the photoconductive antennas to generate a THz time domain pulse. Upon using the Fourier Transform, the spectrum of the pulsed THz signal includes frequencies from …

The Age-Dependent Characterization Of The Er-Alpha Positive Breast Cancer Tumor Microenvironment, Katie Marie Hamel

LSU Doctoral Dissertations

In disease states such as cancer, endocrine and paracrine signals from adipose tissue contribute to cancer progression and drug resistance. Young individuals diagnosed with estrogen receptor-alpha positive (ER-a+) breast cancer have an observed increase in resistance to endocrine therapies. This suggests that an alternative estrogen signaling pathway is active within these tumors. Despite this, the effects of stromal age on the endocrine response in breast cancer is not well known. Here, we review and highlight the involvement of the stromal age in both tumorigenesis and physiological wound healing. To identify specific differences between young and aged ER-a+ breast tumors, RNA …

Elucidating Mechanisms Of Metastasis With Implantable Biomaterial Niches, Ryan Adam Carpenter

Doctoral Dissertations

Metastasis is the leading cause of cancer related deaths, yet it remains the most poorly understood aspect of tumor biology. This can be attributed to the lack of relevant experimental models that can recapitulate the complex and lengthy progression of metastatic relapse observed in patients. Mouse models have been widely used to study cancer, however they are critically limited to study metastasis. Most models generate aggressive metastases in the lung without the use of unique cell lines or specialized injection techniques. This limits the ability to study disseminated tumor cells (DTCs) in other relevant metastasis prone tissues. Prolonged observation of …

Higher Tensile Forces Across Cellular Junctions And An Intact Nuclear Linc Complex Is Required For Epithelial Function And Stability, Fnu Vani Narayanan

Theses and Dissertations

Recent advances in three-dimensional (3D) cell culture systems have provided key insights into the understanding of biochemical and physiological states of native tissue. A significant progress in the field of mechanobiology involves measuring cellular traction forces in a more native 3D environment. However, the effects of mechanical forces exerted across cellular junctions and the nuclear LINC complex, in an organized 3D system has not been investigated thus far. Epithelial cells spontaneously form acini (also known as cysts or spheroids) with a single, fluid-filled central lumen, when grown in 3D matrices. The size of the lumen is dependent on apical secretion …

In Vivo Metabolic And Vascular Response To Hypoxia In Twist Knockdown Murine Breast Cancer, Brandon Sturgill

Graduate Theses and Dissertations

Twist transcription factor is often overexpressed in aggressive tumors. Although needed in early embryonic development for organogenesis, Twist is known to induce an epithelial to mesenchymal transition in cells. In cancer, epithelial to mesenchymal transitions can lead to increased motility and invasiveness. It has also been linked to metabolic reprogramming and increased metastatic risk. Furthermore, metabolic preferences can increase proliferation, enhance metastatic potential, and influence the site of metastasis. We hypothesize that Twist directly affects the metabolism of cancer cells. We expect to see in vivo what we have seen in vitro; Twist overexpression should promote a shift away from …

Diffuse Reflectance Spectroscopy To Quantify In Vivo Tissue Optical Properties: Applications In Human Epithelium And Subcutaneous Murine Colon Cancer, Gage Joseph Greening

Graduate Theses and Dissertations

Colorectal cancer is the 4th most common and 2nd deadliest cancer. Problems exist with predicting which patients will respond best to certain therapy regimens. Diffuse reflectance spectroscopy has been suggested as a candidate to optically monitor a patient’s early response to therapy and has been received favorably in experimentally managing other cancers such as breast and skin. In this dissertation, two diffuse reflectance spectroscopy probes were designed: one with a combined high-resolution microendoscopy modality, and one that was optimized for acquiring data from subcutaneous murine tumors. For both probes, percent errors for estimating tissue optical properties (reduced scattering coefficient and …

Eralpha Isoforms Modulate The Tumorigenicity Of 24r,25(Oh)2d3 In Estrogen-Responsive Cancer, Anjali Verma

Theses and Dissertations

Over 200,000 cases of breast cancer are diagnosed every year. Nearly 20% of these patients supplement their diets with some form of vitamin D. This high frequency of vitamin D supplement use may be due in part to research suggesting that cancer patients with higher serum vitamin D₃ levels have better prognoses than patients with low serum vitamin D_3. However, double-blind clinical trials on the efficacy of vitamin D₃ supplementation in breast cancer have been inconclusive. A recent meta-analysis showed evidence of reduced cancer recurrence in patients taking vitamin D₃ supplements who had ‘estrogen receptor positive’ …

The Role Of Kras In Mechanosensing In Non-Small Cell Lung Cancer, Krista M. Powell

Theses and Dissertations

Lung cancer is the number one cause of cancer related death worldwide, with more than 1.6 million fatalities each year. Non-small cell lung cancer (NSCLC) accounts for 80-85% of all lung cancers, with KRAS being one of the most prevalent oncogenic driver mutations. Therapeutic approaches for KRAS-mutated NSCLC have been extensively explored due to the US National Cancer Institute RAS Initiative, but methods of directly targeting KRAS or downstream effectors, such as MEK, still have poor results. Previous reports have shown that KRAS-mutated NSCLC activate distinct receptor tyrosine kinases (RTKs) depending on the epithelial or mesenchymal state. Epithelial-to-mesenchymal transition (EMT) …

Impedance Sensing Of Cancer Cells Directly On Sensory Bioscaffolds Of Bioceramics Nanofibers, Hanan Alismail

Graduate Theses and Dissertations

Cancer cell research has been growing for decades. In the field of cancer pathology, there is an increasing and long-unmet need to develop a new technology for low-cost, rapid, sensitive, selective, label-free (i.e. direct), simple and reliable screening, diagnosis, and monitoring of live cancer and normal cells in same shape and size from the same anatomic region. For the first time on using an impedance signal, the breast cancer and normal cells have been thus screened, diagnosed and monitored on a smart bioscaffold of entangled nanowires of bioceramics titanate grown directly on the surface of implantable Ti-metal and characterized by …

Direct Quantification Of Deubiquitinating Enzyme Activity In Single Intact Cells, Nora Safabakhsh

LSU Doctoral Dissertations

Challenges in drug efficacy occur during the treatment of most types of cancer due to the heterogeneity of the tumor microenvironment. This has led to the development of personalized medicine. Due to the clinical success of the proteasome inhibitors Bortezomib and Carfilzomib in treatment of multiple myeloma, interest has shifted towards molecularly-targeted chemotherapeutics for ubiquitin-proteasome system (UPS). Deubiquitinating enzymes (DUBs) are an essential part of this pathway which have been found to promote Bortezomib resistance in multiple myeloma patients. Unfortunately, there is a lack of specific, high throughput biochemical assays to characterize DUB activity in patient samples before and after …

Developing Droplet Based 3d Cell Culture Methods To Enable Investigations Of The Chemical Tumor Microenvironment, Jacqueline A. De Lora

Biomedical Sciences ETDs

Adaptation of cancer cells to changes in the biochemical microenvironment in an expanding tumor mass is a crucial aspect of malignant progression, tumor metabolism, and drug efficacy. In vitro, it is challenging to mimic the evolution of biochemical gradients and the cellular heterogeneity that characterizes cancer tissues found in vivo. It is well accepted that more realistic and controllable in vitro 3D model systems are required to improve the overall cancer research paradigm and thus improve on the translation of results, but multidisciplinary approaches are needed for these advances. This work develops such approaches and demonstrates that new droplet-based cell-encapsulation …

A Multiscale Modeling Study Of The Mammary Gland, Joseph D. Butner

Biomedical Engineering ETDs

Multiscale, hybrid computer modeling has emerged as a valuable tool in the fields of computational systems biology and mathematical oncology. In this work, we present an overview of the motivations for, and development and implementation of, three hybrid multiscale models of the mammary gland system and early stage ductal carcinoma in situ (DCIS) in the gland. Pubertal mammary gland development was described first using a two-dimensional, lattice-based hybrid agent-based model description of the mammary terminal end bud (TEB), and then with a three-dimensional lattice-free TEB model. Both models implement a discrete, agent-based description of the cell scale, and a continuum, …

Optimizing A Standard Fasting Time For 2-Nbdg Uptake Studies In Murine Breast Cancers, Andrew C. Briley

Biomedical Engineering Undergraduate Honors Theses

Recently, there has been a larger use of 2-NBDG, a fluorescent glucose analog, to study glucose uptake in different cell types. These cell types have ranged anywhere from bacteria to human cancer cells. However, there has yet to be a standard procedure and practice for using 2-NBDG. In this study, our goal is to create a standard fasting time for the cells before introducing 2-NBDG to them. This study uses 4T07 cells, a murine breast cancer cell line, to help optimize this fasting time. These cells were fasted at different time points in order to find the ideal fasting time. …

Extracellular Matrix Control Of Breast Cancer Metastasis And Dormancy, Lauren Barney

Doctoral Dissertations

To metastasize, a cell must travel through circulation to a secondary tissue, and this process causes 90% of all cancer deaths. Although inefficient, metastasis is not random, and only capable seeds in hospitable soils are capable of outgrowing into detectable metastases. The overall hypothesis in this work is that the secondary tissue microenvironment, particularly the extracellular matrix (ECM), mediates metastasis. We posit that the ability of metastatic cells to survive dormancy, exit quiescence, and colonize a tissue depends upon the ability of the soil to sustain survival, and subsequently trigger outgrowth. We created a simple biomaterial platform with systematic control …

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 …

Immunomodulation Of Breast Cancer Cells For Whole Tumor Vaccination, Kristina G. Maxwell

Biomedical Engineering Undergraduate Honors Theses

Hematogenous metastasis causes 90% of breast cancer-related deaths.Current therapies include chemotherapy and irradiation following surgery. These therapies are very harmful to the human body and do not elicit an anti-tumor immune response. To create a novel therapeutic, an autologous vaccine increasing the immunogenicity of non immunogenic breast cancer cell lines has been proposed.

To create this vaccine, 4T1 mouse mammary breast cancer cells have been selected as the desired cell line to treat. They are non immunogenic and highly invasive. In order to increase their immunogenicity, first projected, was the addition of cytokines to 4T1 cells to increase the expression …

The Role Of E-Cadherin Force In The Maintenance Of Homeostasis In Epithelial Acini, Fnu Vani Narayanan

Theses and Dissertations

Numerous three-dimensional model systems have emerged for emulating the biochemical and physiological states of native tissue. Yet little is known about the effects of mechanical forces on cell behavior in the context of an organized tissue structure in three-dimensional cell-culture. Epithelial cells cultured in a three-dimensional environment comprised of extracellular matrix proteins form spheroids of polarized cells. Cellular responses to mechanical cues, generated from dynamic interactions with the extracellular matrix and neighboring cells, are known to influence cellular behavior to a great extent. Previous studies have shown that tumorigenic progression has been frequently linked to the down regulation of E-cadherin, …

Mimicking The Arterial Microenvironment With Peg-Pc To Investigate The Roles Of Physicochemical Stimuli In Smc Phenotype And Behavior, William G. Herrick

Doctoral Dissertations

The goal of this dissertation was to parse the roles of physical, mechanical and chemical cues in the phenotype plasticity of smooth muscle cells (SMCs) in atherosclerosis. We first developed and characterized a novel synthetic hydrogel with desirable traits for studying mechanotransduction in vitro. This hydrogel, PEG-PC, is a co-polymer of poly(ethylene glycol) and phosphorylcholine with an incredible range of Young’s moduli (~1 kPa - 9 MPa) that enables reproduction of nearly any tissue stiffness, exceptional optical and anti-fouling properties, and support for covalent attachment of extracellular matrix (ECM) proteins. To our knowledge, this combination of mechanical range, low …

Inhalable Nanocomposites And Anticancer Agents For Cancer Therapy, Nathanael A. Stocke

Theses and Dissertations--Chemical and Materials Engineering

Cancer is designated as the leading cause of mortality worldwide and lung cancer is responsible for nearly 30% of all cancer related deaths. Over the last few decades mortality rates have only marginally increased and rates of recurrence remain high. These factors, among others, suggest the need for more innovative treatment modalities in lung cancer therapy. Targeted pulmonary delivery is well established for treating pulmonary diseases such as asthma and provides a promising platform for lung cancer therapy. Increasing local deposition of anticancer agents (ACAs) and reducing systemic exposure of these toxic moieties could lead to better therapeutic outcomes and …

Dispersion Of Cytotoxic Properties Of Multi-Walled Carbon Nanotubes Suspended In Biological Solutions With Tween 80: Their Role In Enhancing Killing Effects Of Nanosecond Pulse Electric Fields On Tumor Cell Lines, Bhargava S. Kalluri

Biological Sciences Theses & Dissertations

The objective of this study was to determine whether multi-walled carbon nanotubes (MWCNTs) suspended in the surfactant Tween 80 give an additive killing effect on tumor cells when exposed to nsPEFs. In this study, MWCNTs were suspended in DMEM and RPMI with or without T80 (surfactant). The size distribution of MWCNTs suspended in these solutions was evaluated with a Delsa™ Nano Zeta potential and sub micro particle Size Analyzer and confirmed with microscopy. The cytotoxicity of MWCNTs dispersed in different concentrations of T80 was evaluated in PANC1 (Human pancreatic cancer cell line) and Jurkat cell lines (Human T-cell lymphoblast cell …

Prostate Cancer Biomarker Identification: A Comparative Study, Wenjuan Jiang

Computational Modeling & Simulation Engineering Theses & Dissertations

With the current development of proteomics techniques, the discovery of potential molecular biomarkers for early detection of prostate cancer has been greatly improved. In this thesis, we implemented five classifiers including the support vector machine (SVM), Bayesian Classifier, Decision Tree, Random Forest and the Multilayer perceptron (MLP) to test their effectiveness in prostate cancer biomarker identification using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) tissue imaging data. The classifiers were utilized to discriminate cancer mass spectra from normal ones for the data collected at the Eastern Virginia Medical School (EVMS). There are 94 7 spectra from normal tissues and 27 from …