Digital Commons Network^™

Shape Memory Alloy Capsule Micropump For Drug Delivery Applications, Youssef Mohamed Kotb

Theses and Dissertations

Implantable drug delivery devices have many benefits over traditional drug administration techniques and have attracted a lot of attention in recent years. By delivering the medication directly to the tissue, they enable the use of larger localized concentrations, enhancing the efficacy of the treatment. Passive-release drug delivery systems, one of the various ways to provide medication, are great inventions. However, they cannot dispense the medication on demand since they are nonprogrammable. Therefore, active actuators are more advantageous in delivery applications. Smart material actuators, however, have greatly increased in popularity for manufacturing wearable and implantable micropumps due to their high energy …

Microwave Imaging Technique For Breast Cancer Detection, Nure Alam Chowdhury

Theses and Dissertations

Breast cancer is a global problem, and it is inevitable to detect cancerous cells at early stages. In recent years, microwave imaging technology has been widely applied in biomedical applications for its non-ionizing radiation. In this study, we design a micro-strip patch antenna with an inverted T-type notch in the partial ground to detect tumor cells inside the human breast. The size of the current antenna is small enough (18 mm × 21 mm × 1.6 mm) to distribute around the breast phantom. The operating frequency has been observed from 6–14 GHz with a minimum return loss of −61.18 dB …

Cancer Treatment By Targeting Hdac4 Translocation Induced By Microsecond Pulsed Electric Field Exposure: Mechanistic Insights Through Kinases And Phosphatases, Zahra Safaei

Theses and Dissertations

Epigenetic modifications, arising from sub-cellular shifts in histone deacetylase (HDAC) activity and localization, present promising strategies for diverse cancer treatments. HDACs, enzymes responsible for post-translational histone modifications, induce these epigenetic changes by removing acetyl groups from ε-N-acetyl-lysine residues on histones, thereby suppressing gene transcription. Within the HDAC group, class IIa HDACs are notable for their responsiveness to extracellular signals, bridging the gap between external stimuli, plasma membrane, and genome through nuclear-cytoplasmic translocation. This localization offers two significant mechanisms for cancer treatment: nuclear accumulation of HDACs represses oncogenic transcription factors, such as myocyte-specific enhancer factor 2C (MEF2C), triggering various cell death …

Magnetic Softness Tuned Superparamagnetic Nanoparticles For Highly Efficient Cancer Theranostics, Jie Wang

Theses and Dissertations

Magnetic resonance imaging (MRI)-guided magnetic nanofluid hyperthermia (MNFH) using iron oxide based superparamagnetic nanoparticles (SPNPs) has recently attracted considerable attention as a treatment modality for cancer theranostics, because MRI-guided MNFH can allow for diagnosis, therapeutics, and prognosis simultaneously using the same administrated magnetic nanofluid agent. However, several primary limiting factors: (1) insufficient AC magnetic heating induction (specific loss power/intrinsic loss power, SLP/ILP) at the biologically safe and physically tolerable range of AC magnetic field (H_AC,safe: f_appl × H_appl < 3.0 ~ 5.0×10⁹ A·m^-1·s^-1), (2) low _r2- relaxivity directly related to the low resolution of …

Long Non-Coding Rna Pvt1 – An Exploratory Study In Ovarian And Endometrial Cancer, Kevin Tabury

Theses and Dissertations

Gynecological cancers, ovarian and endometrial cancer, are still leading causes of cancer-related death in women worldwide. Early detection methods as well as treatment resistance remain a challenge. Long non-coding RNAs (lncRNAs) are emerging as therapeutic targets with diagnostic and prognostic potential with lncRNA PVT1 being one of them.

Here I test and demonstrate the role of PVT1 in ovarian cancer growth and metastasis. PVT1 is amplified and overexpressed in ovarian cancer and has predictive value for survival and response to targeted therapeutics. We find that expression of PVT1 is regulated by tumor cells in response to cellular stress, particularly loss …

Interrogating The Role Of Ing4 In Hematopoietic Stem Cells And Cancer, Zanshé Thompson

Theses and Dissertations

We recently identified the tumor suppressor, Ing4, as a critical regulator of hematopoietic stem cell (HSC) homeostasis. The mis-regulation of Ing4 in human cancers has also been shown to lend malignant cells specific advantages that support carcinogenesis and tumor progression. This activity is, in part, due to Ing4 mediated regulation of overlapping signaling pathways that regulate stem cell activity and cancer cells, including NF-B and c-Myc. In a two-part study, we have investigated the role of Ing4 in murine hematopoiesis and human malignancies. While the specific mechanisms of stem cell self-renewal, maintenance, and differentiation are poorly characterized, we have determined …

Novel Microfabricated Systems To Elucidate The Role Of Anisotropic Stiffness In The Tumor Microenvironment, Jiten Narang

Theses and Dissertations

Cancer is the second leading cause of death in women and late stage (metastatic) cancers have abysmal survival rates compared to early stage regional cases (27% vs 86%). As a tumor grows, the surrounding extracellular matrix (ECM) is reorganized into a dense, collagen rich matrix. The new matrix of aligned collagen fibers provides unique mechanical cues such as anisotropic stiffness and contact guidance. Matrix turnover also constricts local vasculature and restricts delivery of key nutrients and signaling molecules to malignant cells to outside the tumor creating a chemotactic gradient from outside to inside. In this work, we developed a novel …

Cis-Resveratrol Upregulates Tyrosyl-Trna Synthetase And Inhibits The Proliferation Of Select Breast Cancer Cell Lines, Marion Cone Hope Iii

Theses and Dissertations

Breast cancer is one of the most commonly occurring cancers in women. 70% of breast cancer patients express ERα and are treated with tamoxifen (Tam), a drug that is used to directly target ERα. However, 20-30% of cancer patients develop a resistance to Tam. This resistance leads to a worse prognosis and other treatments such as DNA damaging drugs or radiation to eliminate these cells. Resveratrol (RSV) is a polyphenolic- compound found in plants such as grapes and hellebore and is known to evoke anti-cancer effects. While natural resveratrol exists as a mixture of both cis- and trans- isomers, so …

The Use Of Natural Anthraquinone Emodin As A Primary And Complementary Therapeutic In The Treatment Of Colorectal Cancer, Alexander-Jacques Theodore Sougiannis

Theses and Dissertations

5 Fluorouracil (5FU) chemotherapy is widely used in the treatment of colorectal cancer (CRC), and has been the first-choice chemotherapy drug for CRC for many years. However, nearly 10% of patients receiving chemotherapy die during the first 30 days of treatment. Further, it is estimated that 70% of surviving patients will develop non-specific toxicities as a result of chemotherapy treatment. We characterize these toxicities in an animal model of chemotherapy treatment and show that perturbations in the gut microbiome might be exacerbate the prolonged effects of chemotherapy. A compound that could attenuate the multiple non-selective toxicities associated with chemotherapy could …

The Use Of Multi-Targeting Natural Products For The Treatment Of Cancer, Wesley Taylor

Theses and Dissertations

The paradigm shift in cancer treatments from traditional chemotherapeutics to targeted therapies has rapidly improved prognoses for patients for whom cancer was once a death sentence. This is especially true in the case of targeted immune therapies which activate the body’s own natural defense system to fight cancer. Despite these advances, however, cancer remains the second leading cause of death in the United States. The promise of targeted therapeutics has faced significant hurdles in providing effective cancer treatments, namely the limited percentage of susceptible cancers for each treatment, high cost burden, high toxicities, and significant risk of treatment induced resistance. …

High Throughput Analysis Of The Penetration Of Iron Oxide/Polyethylene Glycol Nanoparticles Into Multicellular Breast Cancer Tumor Spheroids, Jonathan Robert Gabriel

Theses and Dissertations

The purpose of this study was to design and optimize a system for the high-throughput analysis of multicellular tumor spheroids (MCTS), and validate the system through the study of a complex biological model. The system was successfully created and optimized, allowing the histological recovery of MCTS at rates up to 90% for microarrays of 24-spheroids. Arrays of 96-spheroids were recovered at rates up to 86%. The system was used to study the penetration of 5k Da-polyethylene coated superparamagnetic iron-oxide nanoparticles (5k-PEG SPIONs) into HTB-126 breast cancer spheroids cultured to a mean diameter of 486 micrometer (± 25.2 micrometer). Results were …

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 3-D Finite Difference Time Domain Investigation Of Microwave Propagation Through Inhomogeneous Biological Materials, David B. Dunn Jr.

Theses and Dissertations

This paper extends past analysis of an optimal source distribution around a homogeneous sphere of muscle tissue by using a 3-D finite difference time domain (FDTD) scenario in which an anatomically correct human head model is irradiated. It first duplicates the analytical solution within an FDTD space using an FDTD computer code developed at Penn State University. This duplication uses a 9.45 cm radius sphere represented in an FDTD space of 2.35 mm cubic cells. FDTD simulations are then performed on four, three, and two layer laminated spheres, designed to provide simple models of a head. Finally, four simulations were …