Digital Commons Network^™

Repositioning Propranolol To Block Mitogenic Signaling In Breast Cancer, Alexa Noel Montoya

Open Access Theses & Dissertations

Breast cancer is the second most diagnosed cancer among women and is about 30% of all new cases of female cancers each year. It is projected that 1 in 8 every U.S. woman (about 13%) develop invasive breast cancer over the course of her lifetime. While advances in cancer research have made it possible to elucidate several breast cancer genomic subtypes, and develop new novel therapies, many of these agents are associated with significant toxicity, as well as high costs. A retrospective cross-sectional study of 404 breast cancer patients was performed to determine the effect of β-blocker usage on tumor …

Biomarkers In Borrelia Burgdorferi Infected Triple-Negative Breast Cancer Cells, Sambuddha Paul

Master's Theses

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited treatment options and a poor prognosis. Although some studies have attempted to identify new biomarkers and therapies, only a few have shown promise in clinical trials. In the context of cancer development, infectious agents rank as the third major risk factor, contributing to approximately 15-20% of cancer cases, according to the American Cancer Society. Hence, the identification of biomarkers associated with infection-originated cancer is crucial for enhancing cancer prevention, early detection, diagnosis, and treatment. Borrelia burgdorferi, the causative agent of Lyme disease, has been linked to TNBC …

Surface Engineering And Microfabrication Of Pdms-Based Devices For Women’S Health Applications, Jamar Hawkins

Doctoral Dissertations

Poly(dimethylsiloxane) (PDMS) is a widely used polymer in biomedical and microfluidics research due to its optical transparency, castability, gas permeability, and relative biocompatibility. However, while the favorable intrinsic properties of the polymer are typically suitable for preventing experimental artifacts, the true advantage of these devices often comes from their customized patterning and design, which can be tailored to specific applications. Critical parameters in biomedical applications such as chemical concentration profiles, fluid streamlines, substrate topography, and mechanical stiffness can all be fine-tuned simply by selecting the appropriate dimensions and arrangement of PDMS microstructures. To address challenges in expanding the application of …

Exposure To Endocrine Disrupting Chemicals And The Effects On Inflammation And Mammary Tumor Progression, Stephanie Morin

Doctoral Dissertations

The vast majority of breast cancers, ~70%, are not directly related to an inherited genetic mutation. Environmental factors play a dominant role in the etiology of most breast cancers. There is a subset of chemicals that are able to affect the homeostasis of hormones called endocrine disrupting chemicals (EDCs). Many of these chemicals are pervasive and persistent making the chances for lifetime exposure more prevalent. While many of these chemicals have been deemed safe, a subset of them have come under review to reassess their safety. As estrogen is critical for breast development and can act as a mitogen in …

Screening Tcf19 And Kif18b To Determine Co-Regulation With Mybl1 In Triple Negative Breast Cancer Patient Tissues, Tyra Sharda Ivory

Theses (2016-Present)

The aggressive behavior in triple-negative breast cancer (TNBC) is due to genetic signaling events, which call for the comprehensive analyses of genes differentially regulated in the cancers. Our laboratory previously found that MYBL1 was over-expressed in a fraction of the TNBC, compared to some luminal, and other breast cancer subtypes. The MYBL1 gene is a proto-oncogene that serves as a strong transcriptional activator. The gene is involved in signaling events related to cell cycle signaling, differentiation, proliferation, and apoptosis, all which are differentially regulated in cancers. Because MYBL1 is a transcription regulator, involved in cancer-related mechanisms and differentially expressed in …

The Roles Of Epithelial–Mesenchymal Plasticity In Tumor Heterogeneity, Metastasis, And Patient Survival In Breast Cancer, Meredith Septer Brown

Dartmouth College Ph.D Dissertations

The Epithelial-to-Mesenchymal transition, a critical cellular process in development, is frequently co-opted by solid tumors to promote invasion and metastasis. In particular, the hybrid or intermediate EMT state, possessing both epithelial and mesenchymal characteristics, is associated with increased cancer stemness and plasticity. Similarly, intra-tumoral heterogeneity in solid tumors, in particular breast cancer, is associated with poor prognosis, tumor growth, proliferation, drug resistance, and metastasis. We sought to understand the link between the generation of intra-tumoral heterogeneity and the intermediate EMT state and their impact on tumor progression and patient prognosis. As part of my thesis work, I developed a model …

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 …

Elucidating The Role Of Kmt2d In Her2+ Breast Cancer, Emily Ma

Dissertations

Breast cancer is the second leading cause of cancer-related deaths among women in the US. Histone modifications are common epigenetic changes that have been implicated in several breast cancers, including HER2+ breast cancers. Current therapies, such as trastuzumab, block the HER2 receptor to reduce tumor growth. Unfortunately, HER2+ breast cancers have found ways to overcome these therapies, leading to tumor resistance, metastases, and poor survival outcomes. A better understanding of the underlying mechanisms contributing to HER2+ breast cancer resistance may lead to the discovery of novel therapeutic strategies to improve patient outcomes.One prognostic marker for poor survival in women with …

The Role Of Cpeb2 Alternative Splicing In Tnbc Metastasis, Shaun C. Stevens

USF Tampa Graduate Theses and Dissertations

Breast cancer is the second leading cause of cancer-related deaths for women in the U.S. Although the overall 5-year survival rate for breast cancer is 90%, this rate drops substantially for triple-negative breast cancer (TNBC) due to its high metastatic potential. Furthermore, there is a lack of targeted therapeutics for TNBC, and clinical trials have been largely unsuccessful. These characteristics validate the need for identifying novel therapeutic targets for the treatment of TNBC. The study of alternative splicing (AS) has emerged as a powerful tool to elucidate the molecular underpinnings driving cancer.

Our lab has identified cytoplasmic polyadenylation element-binding protein …

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 …

Clinical Significance, Functional Role And Molecular Mechanism Of 2’-O-Methyltransferase Ftsj3 In Promoting Cancer Progression, Morenci Manning-Powell

Wayne State University Dissertations

2’-O-methylation (2’-O-Me), one of the most common modifications within RNA, has multiple roles in modulating RNA structure, stability, and interactions, as well as gene transcription and translation. We previously performed integrative genomic and transcriptomic analysis of 58 RNA methyltransferases, and identified FTSJ3 (FtsJ RNA 2ʹ-O-methyltransferase 3) as significantly amplified/overexpressed in breast cancer. Knockdown of FTSJ3 inhibits breast cancer cell growth in vitro. However, the clinical significance, functional role, and molecular mechanism of FTSJ3 in human cancer remains to be elucidated. In the present study, we first analyzed the differential mRNA and protein expression of FTSJ3 between tumor and normal tissues …

Tgfbeta1 And Stat3 As Regulators Of The Ha Synthesis And Signaling Pathway, Brenda Goretty Trevizo

Legacy Theses & Dissertations (2009 - 2024)

The studies described here explored the role of Transforming Growth Factor Beta-1 (TGFβ1) and Signal Transducer and Activator of Transcription 3 (STAT3) as potential regulators of the Hyaluronic Acid (HA) synthesis and signaling pathway in human mammary cells. Our results support previous findings in which TGFβ1, a well characterized driver of the epithelial-mesenchymal transition (EMT) has been shown to regulate HA synthesis and signaling. Interrogation of The Cancer Genome Atlas (TCGA) indicated HAS2 expression positively correlated with TGFβ1 mRNA expression in breast cancer patients and in breast cancer cell lines. RT-qPCR experiments were used to measure the expression of the …

Cold-Inducible Rna Binding Protein (Cirp) Impedes Proliferation And Inflammation In The Pymt Mouse Model For Breast Cancer, Daniel Albino Lujan

Biomedical Sciences ETDs

RNA binding proteins (RBPs) regulate gene expression by controlling mRNA export, translation, and stability. When altered, some RBPs allow cancer cells to grow, survive, and metastasize. Cold-inducible RNA binding protein (CIRP) is overexpressed in a subset of breast cancers, induces proliferation in breast cancer cell lines, and inhibits apoptosis. We generated a transgenic mouse model overexpressing human CIRP in the mammary epithelium to ask if it plays a role in mammary gland development. We also assessed the effects of CIRP on breast tumorigenesis using breeding crosses with the PyMT mouse model for breast cancer. CIRP decreased proliferation at the lactational …

The Role Of Reactive Oxygen Species In Regulating Macrophage And Fibroblast Activation Within The Breast Cancer Tumor Microenvironment, Brandon J. Griess

Theses & Dissertations

The tumor microenvironment (TME) is a key determining factor in breast cancer, especially the more aggressive subtype triple negative breast cancer (TNBC). The activated fibroblasts and macrophages within the TME have many tumor promoting functions. Therefore, targeting their activation presents a novel therapeutic approach in TNBC. My work studied the role of reactive oxygen species (ROS) during fibroblast and macrophage activation in breast cancer.

My studies showed that expression of the secreted antioxidant enzyme, EcSOD, is silenced in breast cancer samples, in part, via increased promoter methylation. The re-expression of EcSOD inhibited c-Met activation in the TNBC cell line, MDA-MB231. …

Regulatory T Cells Promote Breast Cancer Progression Through Inhibiting Classical Activation Of Macrophages, Nicholas M. Clark

Theses and Dissertations

Transient ablation of regulatory T cells has been shown to be effective at hindering tumor growth and metastasis in murine breast cancer model. Based on our lab’s previous work, we have demonstrated that NK cells and CD8+ cytotoxic T cells were not required for the protective effect of Treg cell ablation. However, we also reported that CD4+ helper T cells and IFN-γ were required for the protective effect of Treg cell ablation. Furthermore, we observed that CD11B+ cells responded to Treg ablation therapy by up-regulating target genes of IFN-γ. Therefore, this study aimed to investigate the connection between the myeloid …

Microenvironment Regulates Fusion Of Breast Cancer Cells, Peiran Zhu

Masters Theses

Fusion of cancer cells has been observed in tumors for more than a century and is thought to contribute to tumor development and drug resistance. The low frequency of cell fusion events and the instability of fused cells have hindered our ability to understand the molecular mechanisms that govern cell fusion. We have developed a patterned gel system that can isolate cell fusion events and we demonstrate that several breast cancer cell lines can fuse into multinucleated giant cells in vitro, and the initiation and longevity of fused cells can be regulated solely by biophysical factors. Dynamically tuning the adhesive …

Molecular And Biochemical Studies Of Several Novel Estrogen Receptor Alpha-Interacting Proteins In Breast Cancer Cells, Ahmed Edan Dhamad

Graduate Theses and Dissertations

Breast cancer is the second leading cause of cancer-related death in women, and approximately 70% of incidences are estrogen receptor (ER)-positive breast cancer. ERα and its interacting proteins play a key role in the development and progression of breast cancer. However, how ERα regulates its target gene expression and hence cell proliferation is not fully understood. To enhance our understanding of the molecular mechanism by which ERα regulates gene expression, we used a quantitative proteomic method to identify cellular proteins that interact with ERα. The first group of proteins that were identified to associate with ERα are heat shock proteins …

The Role Of Cytoplasmic Polyadenylation Element Binding Protein -2 (Cpeb-2) In Human Breast Cancer, Joshua Tordjman

Electronic Thesis and Dissertation Repository

Cyclooxygenase-2 (COX-2) is overexpressed in 40-50% of breast cancers, and promotes tumour progression through increased proliferation, migration, invasion, Epithelial-to-Mesenchymal Transition (EMT), and induction of therapy-resistant Stem-Like-Cells (SLCs). COX-2 stimulates expression of two oncogenic and SLC-promoting microRNAs (miR-526b, miR-655), which simultaneously target one gene, Cytoplasmic Polyadenylation Element Binding Protein-2 (CPEB-2). Hypothesis: CPEB-2 is a tumour- and SLC-suppressing gene in breast cancer. Results: CPEB-2 knockout in a non-tumourigenic mammary epithelial cell line MCF10A demonstrated increases in proliferation, migration, invasion, EMT markers, SLC content, and VEGF-D expression. CPEB-2, an mRNA-binding translation-regulating protein, was found to regulate the translation of tumour suppressor p53. When …

Regulation Of Breast Cancer Initiation And Progression By 14-3-3zeta, Chia-Chi Chang

Dissertations & Theses (Open Access)

14-3-3ζ is a ubiquitously expressed family member of proteins that have been implicated to have oncogenic potential through its interactions and involvement in cancer initiation and progression. 14-3-3ζ belongs to the highly conserved 14-3-3ζ protein family and modulates numerous pathways in cancer. Overexpression of 14-3-3ζ is an early event, occurs in more than 40% of human breast cancer cases, and is associated with disease recurrence and poor prognosis. Metabolic reprogramming is a hallmark of cancer. Cancer cells elevate aerobic glycolysis to produce metabolic intermediates and reducing equivalents, thereby facilitating cellular adaptation to the adverse environment and sustaining fast proliferation. Interestingly, …

The Roles Of Malt1 In Nf-Κb Activation And Solid Tumor Progression, Deng Pan

Dissertations & Theses (Open Access)

The transcription factor NF-κB plays a central role in many aspects of biological processes and diseases, such as inflammation and cancer. Although it has been suggested thatNF-κB is critical in tumorigenesis and tumor progression, the molecular mechanism by which NF-κB is activated in solid tumor remains largely unknown. In the current work, we focus on growth factor receptor-induced NF-κB activation and tumor progression, including epidermal growth factor receptor (EGFR)-induced NF-κB in lung cancer and heregulin receptor (HER2)-induced NF-κB in breast cancer. We found that Mucosa-associated lymphoma translocation protein 1 (MALT1), also known as paracaspase, is required for EGFR-induced NF-κB activation …

Functional Regulation Of Yap By Aurora A Kinase In Triple-Negative Breast Cancer, Shih-Shin Chang

Dissertations & Theses (Open Access)

The Yes-associated protein (YAP) is an effector that transduces the output of the Hippo pathway to transcriptional modulation. Considering the role of YAP in cancers, this protein has emerged as a key node in malignancy development. In this study, we determined that Aurora A kinase acts as a positive regulator for YAP-mediated transcriptional machinery. Specifically, YAP associates with Aurora A predominantly in the nucleus. Activation of Aurora A can impinge on YAP activity through direct phosphorylation. Moreover, aberrant expression of YAP and Aurora A signaling is highly correlated with triple-negative breast cancer (TNBC). We herein provide evidence to establish the …

Uncovering New Roles For The Aryl Hydrocarbon Receptor (Ahr) In Breast Cancer, Justin Kirk Tomblin

Theses, Dissertations and Capstones

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that is responsive to many exogenous and endogenous ligands. AHR is of particular interest in cancer, and has been shown to play roles in tumor progression. As such, it has received growing attention as a possible chemotherapeutic target. Obesity increases the risk of breast cancer, complicates treatment of breast cancer, and stimulates the growth of larger, more aggressive mammary tumors. Many breast tumors in obese women are estrogen receptor (ER)-positive and, while targeting hormone receptors like ER is beneficial, many obese women see a recurrence of their cancer after standard …

Effect Of Cmvil-10 On Exosome Production By Human Breast Cancer Cells, Susanna N. Basappa

Undergraduate Honors Theses

Human cytomegalovirus (HCMV) is a ubiquitous virus that infects 70-90% of the general population, primarily the immunocompromised, but has been implicated in several forms of cancer, including breast cancer. Breast cancer is the second leading cause of cancer related deaths in women in North America, usually from metastasis. Exosomes are 30-100nm vesicles produced by most cells which carry protein and RNA to cells in their microenvironment. The aim of this study is to investigate the impact of HCMV-infection of a secreted viral cytokine, cmvIL-10, on exosome production by highly metastatic breast cancer cells.

MDA-MB-231 cells were cultured in vitro, …

The Influence Of Matrix Stiffness On Extracellular Matrix Protein Expression In 3d Encapsulated Mammary Fibroblasts, Kathryn Woods

PCOM Biomedical Studies Student Scholarship

A disease that transcends all races is breast cancer, the second leading cause of death among women with cancer. One factor, which participates in breast tumor progression, is the extracellular matrix (ECM), an acellular, protein-rich entity, which drives several cell, processes shown to promote tumorigenesis. Specifically, abnormal expression patterns and cross-linking of matrix fibers induces a more dense tissue structure, which has been reported to drive breast cancer progression. Alterations in ECM expression and cross-linking are in part due to carcinoma-associated fibroblasts (CAFs), activated fibroblasts which deposit copious ECM in the breast tumor environment. The goal of this study is …

Immunotherapy Of Cancer: Reprogramming Tumor/Immune Cellular Crosstalk To Improve Anti-Tumor Efficacy, Kyle K. Payne

Theses and Dissertations

Immunotherapy of cancer has been shown to be promising in prolonging patient survival. However, complete elimination of cancer and life-long relapse-free survival remain to be major challenge for anti-cancer therapeutics. We have previously reported that ex vivo reprogramming of tumor-sensitized immune cells by bryostatin 1/ionomycin (B/I) and the gamma-chain (γ-c) cytokines IL-2, IL-7, and IL-15 resulted in the generation of memory T cells as well as CD25+ NKT cells and CD25+ NK cells. Adoptive cellular therapy (ACT) utilizing these reprogrammed immune cells protected FVBN202 mice from tumor challenge, and overcame the suppressive functions of myeloid-derived suppressor cells (MDSCs). We then …

Kiss1r Signaling Promotes Breast Cancer Metastasis, Cameron G-F Goertzen

Electronic Thesis and Dissertation Repository

Kisspeptins, peptide products of KISS1, are endogenous ligands for KISS1R, a G protein-coupled receptor. In numerous cancers, KISS1 acts as a metastasis suppressor. However, studies have revealed that patients with elevated KISS1 and KISS1R breast tumor expression have increased tumor grade, increased lymph node metastases and poor survival. We hypothesize that depletion of KISS1R inhibits breast cancer cell metastasis. In order to assess the role of KISS1R in breast cancer metastasis, we used a pre-clinical orthotopic xenograft mouse model using MDA-MB-231 breast cancer cells for breast tumor establishment. We discovered that depletion of KISS1R decreased primary tumor growth and …

Imbalance Between Neutrophil Elastase And Elafin Promotes Breast Cancer Growth And Progression, Joseph Anthony Caruso

Dissertations & Theses (Open Access)

Elafin, an endogenous serine protease inhibitor, is a critical component of the epithelial barrier against neutrophil elastase (NE) activity. The central hypothesis examined in this dissertation was that elafin has tumor suppressive properties in breast cancer. In support of this hypothesis, immunohistochemical (IHC) analysis revealed that elafin was downregulated in the majority of invasive breast tumors and a subset of pre-invasive ductal carcinoma in situ (DCIS) compared to elafin expression in the normal mammary epithelium. To understand the role of elafin in the mammary epithelium and the impetus for its downregulation during breast tumorigenesis, primary and immortalized human mammary epithelial …

Investigation Of Rice Bran Derived Anti-Cancer Pentapeptide For Mechanistic Potency In Breast Cancer Cell Models, Ruiqi Li

Graduate Theses and Dissertations

Bioactive peptides derived from food sources with anti-proliferative properties against cancer have drawn more attention in recent years. A pentapeptide derived from rice bran has shown anti-proliferative propertiesagainst human breast cancer cells. The objective of this study was to investigate the mechanistic action of the pentapeptide-induced apoptosis in breast cancer cell models (MCF-7 and MDA-MB-231). The growth inhibition activity of the pentapeptide was

evaluated by MTS[3-(4,5-dimethylthiazol-2-yl)-5-(3- arboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt] assayand trypan blue assay in a dose- and time-dependent manner.

The apoptotic properties of pentapeptide-induced apoptosis on cancerous breast cells were evaluated by morphological changes, DNA fragmentation, and caspases-3/7, -8,and -9 …

Arachidonic Acid Signaling In Invasive And Non-Invasive Breast Cancer Cells, Debarshi Roy

Open Access Theses & Dissertations

Breast cancer is the second largest cause of cancer-related deaths in women all over the world. Epidemiological studies suggest that the consumption of high-fat diets can promote the incidence of breast cancers in both developed and developing countries. In particular, the lipid-rich diet contains arachidonic acid (AA, a C20:4 polyunsaturated fatty acid), which has been shown to be associated with tumor formation in breast tissues. Nevertheless, the actual mechanism by which AA induces the metastatic transformation and malignancy is not well understood. The goal of my dissertation, therefore, is to identify the molecules and unravel the pathways that participate in …

Suppression Of Chronically Induced Breast Carcinogenesis And Role Of Mesenchymal Stem-Like Cells, Kusum Rathore

Doctoral Dissertations

Sporadic breast cancers are mainly attributable to long-term exposure to environmental factors, via a multi-year, multi-step, and multi-path process of tumorigenesis involving cumulative genetic and epigenetic alterations in the chronic carcinogenesis of breast cells from a non-cancerous stage to precancerous and cancerous stages. Epidemiologic and experimental studies have suggested that various dietary compounds like green tea and grape seed may be used as preventive agents for breast cancer control. In this research, I have developed a cellular model that mimics breast cell carcinogenesis chronically induced by cumulative exposures to low doses of environmental carcinogens. I used the chronic carcinogenesis model …