Digital Commons Network^™

The Role Of Orphan Nuclear Receptor Dax-1 (Nr0b1) In Human Breast Cancer Cells: Expression, Proliferation And Metastasis, Erin Dishington

Master's Theses

The orphan nuclear hormone receptor DAX-1 (Dosage Sensitive Sex Reversal, Adrenal Hypoplasia Congenita on the X Chromosome, gene 1) plays an important role in the development of adrenal and gonadal tissues and functions as a global negative-regulator of steroidogenesis. In addition, it is known to be involved in several diseases including some cancers. Herein, we describe our examination of the role of DAX-1 in breast cancer, specifically its influence on proliferation and metastasis and its expression during progressive stages of disease. In an effort to understand how DAX-1 influences breast cancer cell proliferation and metastasis, we used MCF7 breast cancer …

Intraoperative Photoacoustic Imaging Of Breast Cancer, Ivan Kosik

Electronic Thesis and Dissertation Repository

Breast cancer is one of the most common cancers to affect women, presenting a lifetime risk of 1 in 8. Treatment of stage 1 and 2 cancers usually involves breast conserving surgery (BCS). The goal of BCS is to remove the entire tumour with a surrounding envelope of healthy tissue, referred to as a negative margin. Unfortunately, up to 50% of surgeries fail to remove the whole tumour. To minimize the risk of cancer recurrence, a second surgery, must therefore be performed. Currently, there is no widely accepted intraoperative tool to significantly mitigate this problem. Employed systems are usually based …

Oncostatin M Promotes Breast Cancer Metastasis: Increased Expression Of Pro-Angiogenic Factors, Inflammatory Cytokine Expression, And Circulating Tumor Cell Numbers, Ken Tawara

Boise State University Theses and Dissertations

Breast cancer is the most diagnosed cancer type in women and its resultant mortality is second only to lung cancer worldwide. While breast cancer is known to have many risk factors, inflammation remains an unquantifiable risk, and it can arise from obesity, depression, poor health, autoimmune diseases, and other conditions that cause systemic chronic inflammation. Chronic inflammation is gaining recognition for its role in cancer development, the potentiation of a metastatic phenotype in cancer cells, and decreased survival in breast cancer patients. In particular, inflammatory cytokines in the interleukin-6 (IL-6) family have been shown to promote an epithelial-mesenchymal transition (EMT), …

Cytoplasmic Cyclin E Mediates Resistance To Aromatase Inhibitors In Breast Cancer, Iman Doostan

Dissertations & Theses (Open Access)

Almost seventy percent of patients with breast cancer have tumors that express hormone receptors and need hormonal therapy. Aromatase inhibitors (AIs) block estrogen biosynthesis and are considered as the first line hormonal therapy for ER⁺ post-menopausal patients. However, resistance to these drugs remains a major challenge in clinic and the biology of such resistance is not completely understood. Cyclin E is deregulated in breast cancer through generation of low molecular weight isoforms that renders patients to a poor survival. Herein, we show that HR+ patients with LMW-E expressing tumors show diminished early response to neo-adjuvant AIs as well as …

A Comprehensive Model And Modulation Of Cellular Signaling Involved In Early Mammary Development And Aggressive Cancer Using A Novel Recombinant Protein Of The G3 Domain Of Laminin-5, Kathryn Adrian Elliott

All Dissertations

The mammary gland is a unique and specialized epidermal organ; mammary organogenesis begins in the embryo but is not fully complete until puberty. As such, formation of the mammary gland depends on temporally and spatially regulated developmental steps that require coordination of multiple biological and cell signaling processes; many of which have parallels with cancer development. Research describing the events that occur between birth and puberty is lacking and little is known about human breast development of youth. Since mammary gland development requires a coordinated balance between cell growth, proliferation, and apoptosis, it is critical to understand which signaling pathways …

Multifunctional Polymeric Micelles For Drug Resistant Breast Cancer: Self-Assembling Poly(Lactide-Co-Glycolide)-Graft-Polyethylenimine, Graham Mackenzie Temples

All Dissertations

Breast cancer is the most common malignancy and the leading cause of cancer death in women. Systemic breast cancer therapies include 1) hormone therapy, 2) immunotherapy, and 3) chemotherapy. Chemotherapy is commonly used in combination with immunotherapy, achieving synergistic activity by multiple mechanisms specific to the type of breast cancer. However, the efficacy of anticancer drugs has been limited by their toxic side effects in normal cells and drug resistance acquired by cancer cells. Therefore, the development of a novel treatment strategy for the selective delivery of therapeutic agents to breast cancer cells is crucial to improve the therapeutic index …

Role Of Human Arylamine N-Acetyltransferase 1 In Tumorigenesis And Cancer Biology., Marcus William Stepp

Electronic Theses and Dissertations

Human arylamine N-acetyltransferase 1 (NAT1) is a well-known phase II metabolic enzyme that has been associated with carcinogenesis. Its role in the biotransformation of aromatic and heterocyclic amine carcinogens has been investigated for many years, but more recent investigations focus on a possible endogenous role of human NAT1 in cancer initiation and progression. To further explore and understand possible endogenous roles for NAT1, we conducted in vitro enzymatic reactions, in vivo studies using homozygous high (rapid) or low (slow) NAT2 activity congenic F344.WKY rats, and genetically modified human breast cancer cell lines. Human NAT1 and rodent NAT2 hydrolyzed acetyl-coenzyme …

Mathematical Modeling For Predicting Chemotherapy And Nanoparticle Treatment Efficacy In Breast Cancer, Terisse Arielle Brocato

Biomedical Engineering ETDs

Breast cancer treatment response varies by subtype, treatment regiment, and additionally by vasculature characteristics. For this reason, breast cancer is a model disease for the development of both targeted therapy and prognostic and predictive biomarkers. Mathematical modeling allows for personalized patient specific prediction of treatment outcome based on parameters found to be important to the cancer type. Mathematical modeling is beneficial in providing insight into why cancer treatment fails and in what cases, additionally determining what characteristics result in a successful treatment. Presented in Chapter 1 is a scientific introduction and discussion focusing on representative modeling works specified towards breast …

Relationship Between Disengagement Coping During Primary Treatment For Non-Metastatic Breast Cancer And Long-Term Depressive Symptoms: The Role Of Pain And Fatigue Interference, Hannah M. Fisher

Open Access Theses

Breast cancer survivors experience significant symptom burden during active treatment and survivorship. Psychosocial factors, such as coping, may influence the course of treatment-related physical and psychological symptomatology. Disengagement coping in particular, may be relevant to breast cancer survivors’ symptom experience. Yet, classification of individual coping responses to comprise a higher order category of disengagement coping remains ambiguous, and research investigating the role of disengagement coping on the trajectory of physical and psychological symptoms in breast cancer survivors has yielded inconsistent findings. This study aimed to test a mediation model elucidating the longitudinal relationship between a latent construct of disengagement coping …

The Fight Against Breast Cancer: A Policy And Programmatic Approach, Nandi Robinson

Master's Projects and Capstones

Abstract

Breast cancer continues to remain a significant health issue for women. Previously thought to only occur among postmenopausal women, breast cancer has impacted women of different ages; and rates of breast cancer have various impacts among different ethnic groups. For women living in a toxic environment, many of them have become the new wave of breast cancer cases. Screening and detection have succeeded in decreasing mortality rates. However, more research is needed in finding an efficient method of treatment. In the effort to assist in the fight against breast cancer through a policy and programmatic angle, I am fulfilling …

The Role Of P16 In Controlling Mammary Epithelial Cell Senescence And Brca1-Deficient Tumorigenesis, Alexandria Scott

Open Access Dissertations

A major risk factor of breast cancer is aging. Aging is caused partly by cellular senescence, a tumor suppressive mechanism that prevents the proliferation of cells at risk of transformation. p16INK4A (p16), an inhibitor of CDK4 and CDK6, plays a critical role in controlling senescence. Functional inactivation of p16 is frequently detected in human breast cancers. However, loss of p16 alone in mice does not result in mammary tumorigenesis. How p16 loss contributes to mammary cell aging and tumorigenesis in vivo is not fully understood. We reported that senescence was induced in mammary epithelial cells (MECs) during aging with increased …

Analysis Of Ngs Data From Immune Response And Viral Samples, Ekaterina Gerasimov

Computer Science Dissertations

This thesis is devoted to designing and applying advanced algorithmical and statistical tools for analysis of NGS data related to cancer and infection diseases. NGS data under investigation are obtained either from host samples or viral variants. Recently, random peptide phage display libraries (RPPDL) were applied to studies of host's antibody response to different diseases. We study human antibody response to breast cancer and mouse antibody response to Lyme disease by sequencing of the whole antibody repertoire profiles which are represented by RPPDL. Alternatively, instead of sequencing immune response NGS can be applied directly to a viral population within an …

Early Detection Of Metastatic Cancer Using Computational Analysis, Nuzhat Mansur

Electrical Engineering Dissertations

Metastasis is the leading cause of cancer related deaths. Early detection of cancer cells can enable early disease diagnosis and stage specific therapeutics. Metastatic cancer cells have abnormal expression of certain proteins. One such protein is Epidermal Growth Factor Receptor (EGFR). Anti-EGFR aptamers have emerged as more effective probe molecules for selectively binding with EGFR compared to antibodies. Capturing cancer cells with aptamer is an emerging and developing technique for cancer cell isolation. Nanotextured substrates inspired by naturally occurring basement membranes are promising platform for triggering unique cell behavior. Along with the biochemical and physical techniques to probe cancer cell …

Utilization Of Genomics For Risk Assessment And Molecular Subtyping To Improve Treatment Strategy In Breast Cancer, Lisa Eileen Blumencranz

Open Access Dissertations

Death from breast cancer began a decline in the 1990’s. One widely accepted reason for this reduction was the discovery that breast cancer can be uniquely defined at the molecular level by oncogenes and tumor suppressor genes including, but not limited to, EGFR, AKT, ErbB2, PI3K, TP53, BRCA1/2, and PTEN. These genes and potential mutations within, can drive constitutive activation of aberrant signaling that can induce and sustain tumorigenesis. More importantly, these genes represent new avenues for possible markers and therapies. In the wake of this molecular biology discovery, there was an influx of new breast cancer treatments to the …

Central Precocious Puberty Alters The Mammary Gland Epithelial Landscape In Female Rats, Alina M. Hamilton

Theses and Dissertations

Precocious puberty (PP) is a serious endocrine disorder associated with an increased risk for development of breast cancer (BC) later in life. However, the lack of a strong in vivo model has made it difficult to study this relationship. Our group has established manganese (Mn) as a non-toxic activator of the pubertal process. Recently we demonstrated that Mn-induced precocious puberty (MnPP) accelerates E2-regulated mammary gland (MG) development in prepubertal female rats, resulting in persistent proliferation and adult hyperplasia. Using this model, I demonstrate that precocious puberty alters steroidal regulation of proliferation in both the prepubertal and adult virgin MG, altering …

Depression And Inflammatory Changes After Cognitive-Behavioral Stress Management As Predictors Of Survival And Disease Recurrence In Women With Non-Metastatic Breast Cancer, Laura C. Bouchard

Open Access Dissertations

Both depression and inflammation are independently associated with breast cancer health outcomes, and multiple studies have shown that depression and inflammatory markers may be linked among women with breast cancer. Studies of cognitive-behavioral based psychosocial interventions have found beneficial intervention effects on time to survival and recurrence in breast cancer patients. However, the mechanisms through which interventions affect clinical health outcomes are less understood. It has been suggested that psychosocial interventions may affect long-term breast cancer clinical disease endpoints via effects on immune and inflammatory processes, but more research is necessary to explore these relationships. The current study examined the …

Cognitive Behavioral Stress Management Effects On Social Well-Being, Negative Affect, And Inflammation After Surgery For Breast Cancer, Devika R. Jutagir

Open Access Dissertations

Many women experience distress during diagnosis and treatment of breast cancer, and research suggests that satisfaction with access to social resources both decreases psychological distress and improves duration of survival after breast cancer diagnosis. However, biobehavioral mechanisms linking interpersonal processes to mental and physical health are poorly understood. Studies are also needed to elucidate whether psychosocial interventions that improve social well-being and psychological health affect biological outcomes known to promote cancer disease progression (e.g., inflammation). This study examined a subsample of 78 women enrolled in a 10-week randomized controlled trial of cognitive behavioral stress management (CBSM) at the University of …

The P53 Independent Functions Of Estrogen-Activated Mdm2 In Cell Signaling And Mammary Architecture, Nandini Kundu

Dissertations, Theses, and Capstone Projects

Estrogen receptor positive (ER+) breast cancers often have MDM2 overexpression indicating a critical role for MDM2 in breast cancer tumorigenesis. The cancer genome atlas (TCGA) found that increased MDM2 expression is one of the four pathways that correlate with all breast cancer subtypes. MDM2 is mainly known as the negative regulator of wild type p53. However, aggressive breast cancers often have MDM2 overexpression and mutant p53 (mtp53). We previously reported that MDM2 provides an estrogen-mediated proliferative advantage to MCF-7 breast cancer cells (ER+, MDM2 overexpression, wild type p53), independent of wild type p53 in both 2D and 3D culture conditions. …

Integrative Analysis To Evaluate Similarity Between Brcaness Tumors And Brca Tumors, Weston Reed Bodily

Theses and Dissertations

The term "BRCAness" is used to describe breast-cancer patients who lack a germline mutation in BRCA1 or BRCA2, yet who are believed to express characteristics similar to patients who do have a germline mutation in BRCA1 or BRCA2. Although it is hypothesized that BRCAness is related to deficiency in the homologous recombination repair (HRR) pathways, relatively little is understood about what drives BRCAness or what criteria should be used to assign patients to this category. We hypothesized that patients whose tumor carries a genomic or epigenomic aberration in BRCA1 or BRCA2 should be classified under the BRCAness category and that …

Integrative Analysis To Evaluate Similarity Between Brcaness Tumors And Brca Tumors, Weston Reed Bodily

Theses and Dissertations

The term "BRCAness" is used to describe breast-cancer patients who lack a germline mutation in BRCA1 or BRCA2, yet who are believed to express characteristics similar to patients who do have a germline mutation in BRCA1 or BRCA2. Although it is hypothesized that BRCAness is related to deficiency in the homologous recombination repair (HRR) pathways, relatively little is understood about what drives BRCAness or what criteria should be used to assign patients to this category. We hypothesized that patients whose tumor carries a genomic or epigenomic aberration in BRCA1 or BRCA2 should be classified under the BRCAness category and that …

The Lived Experience Of Chemo Brain In Early Stage Breast Cancer In Women 50 And Under, Patricia A. Gibbons

Seton Hall University Dissertations and Theses (ETDs)

Cognitive deficits have been shown to affect those who have undergone treatment with chemotherapy. This is often referred to as chemo-brain. The purpose of this descriptive phenomenological study was to explore the lived experience of the chemo brain after undergoing chemotherapy for breast cancer. The study sample consisted of six women between the ages of 29 and 50 with early stage breast cancer. van Manen’s (1997) descriptive phenomenological method guided data analysis. The recurrent themes identified in this study were (1) Struggles with day to day life (2) Emotions related to diagnosis and treatment, (3) Fatigue (4) Coping and support, …

Genetic And Molecular Biomarkers Associated With Radiotherapy-Related Pain Among Breast Cancer Patients, Eunkyung Lee

Open Access Dissertations

Breast cancer is the most commonly diagnosed cancer and the second leading cause of cancer death in American women. Compared to surgery alone, post-surgery adjuvant radiotherapy (RT) significantly reduces local-regional recurrence and mortality, and currently there are more than 3.5 million breast cancer survivors in the United States. Therefore, it is important to address quality of life issues related to RT-induced side effects and pain is one of the most prevalent side effects from cancer treatments. However, predictors and molecular mechanisms for the development of RT-related pain in breast cancer survivors have not been well defined. Therefore, to achieve our …

The Role Of Ehd2 In Triple-Negative Breast Cancer Tumorigenesis And Progression, Timothy A. Bielecki

Theses & Dissertations

Triple-negative breast cancer (TNBC) comprises 10%-15% of all breast cancer cases, yet is clinically challenging due to lack of targeted therapies which leads to higher mortality. Molecular subtyping has identified the most aggressive subclasses of breast cancer to be enriched in components of caveolae. While caveolae have been linked to many biological processes, their precise role in TNBC is still poorly understood. EHD2, a member of the C-terminal EPS15-Homology Domain-containing (EHD) protein family, has emerged as a new regulator of caveolae dynamics and is essential to maintain a stable membrane pool of caveolae. Studies in model cells demonstrate that caveolae …

The Role Of Hope And Optimism In Breast Cancer Patients: A Systematic Review, Jennifer Novalany

Master of Social Work Clinical Research Papers

The purpose of this systematic literature review was to explore the question: How does using hope and optimism effect the psychosocial adjustment to a diagnosis of breast cancer in women? The electronic databases used to identify studies for this review included PsycINFO (PsycNet), SocINDEX, and MEDLINE. Five quantitative studies met criteria and were reviewed and analyzed. The four themes that emerged within these studies were; optimism levels, medical and demographic variables, coping strategies, and fear of cancer recurrence. The research shows that differing levels of optimism linked with other coping strategies, such as; focusing on the positive, fighting spirit, active …

Targeting Autophagy To Improve Efficacy Of Cdk4/6 Inhibition In Breast Cancer, Smruthi Vijayaraghavan

Dissertations & Theses (Open Access)

Deregulation of the cell cycle machinery is a hallmark of cancer, leading to aberrant proliferation and tumorigenesis. The crucial role of the CDK4/6-Cyclin D pathway has led to the development and FDA approval (palbociclib, ribociclib) of CDK4/6 inhibitors for the treatment of advanced estrogen receptor positive breast cancer. However, three major clinical challenges remain: i) adverse events leading to discontinuation of therapy and ii) lack of reliable biomarkers to identify responsive patients and iii) acquired resistance to CDK4/6 inhibitors. Previous in vitro studies have shown that palbociclib mediated CDK4/6 inhibition induces G1 arrest and senescence in ER+ breast cancer cells, …

Characterization Of Murine Breast Cancer Cell Lines For Anti-Cancer Vaccine, Haven N. Frazier

Biological Sciences Undergraduate Honors Theses

Breast cancer is the most commonly diagnosed cancer in women and the second leading cause of cancer death among women in the United States (1). While treatments involving radiation and chemotherapy currently exist, disease must be detected early in order for the treatments to be somewhat effective, and there is no effective treatment after metastasis occurs (2). Additionally, current therapies do not mitigate tumor immunosuppression. Decreasing the tumor-associated immunosuppressive conditions while activating antitumor immunity could prevent recurrence and metastasis, possibly leading to an effective treatment for cancer (3). Tumor cell vaccines could possibly address this issue and have become a …

Assessing Women's Attitudes Towards Genetic Testing For Hereditary Breast Cancer, Taylor Jane Apostolico

Theses and Dissertations

OBJECTIVES: Hereditary Breast and Ovarian Cancer (HBOC) is an autosomal dominant cancer predisposition syndrome with a 46-87% lifetime risk of breast cancer. Unaffected women who have HBOC are eligible for more screening procedures and prophylactic surgeries that may reduce the risk of developing cancer by up to 95%. The objectives of this study were to assess women’s awareness of and interest in breast cancer genetic testing services, as well as women’s attitudes and beliefs regarding the clinical utilization of HBOC genetic testing across demographic categories. METHODS: Two-hundred and sixty-eight women completed a 35-item survey designed to capture perceptions of HBOC …

Unthink Pink : Master Narratives And Counterstories Of Breast Cancer., Jessica C. Hume

Electronic Theses and Dissertations

This work examines the construction and impact of the master narrative breast cancer which is supported and reified by the contemporary breast cancer awareness movement. I contend that historical problematic constructions of the female body were interwoven with the beginning of the movement around the turn of the twentieth century. As a partial result, the female body with breast cancer is abject, and therefore subject to policing and discipline. The master narrative of breast cancer, through pinkwashing, enacts this policing and discipline. The master narrative expresses several distinct messages which may be exclusive of the experiences of many people, causing …

Role Of Mir-29b-1 And Mir-29a In Endocrine-Resistant Breast Cancer., Penn Muluhngwi

Electronic Theses and Dissertations

Therapies targeting estrogen receptor α (ERα) including selective estrogen receptor modulators (SERMs), e.g., tamoxifen (TAM); selective estrogen receptor downregulators (SERDs), e.g., fulvestrant (ICI 182,780); and aromatase inhibitors (AI), e.g., letrozole, are successfully used in treating breast cancer patients whose initial tumor expresses ERα. Unfortunately, the effectiveness of endocrine therapies is limited as ~ 40% of breast cancer patients will eventually acquire resistance to them. The role of miRNAs in the progression of endocrine-resistant breast cancer is of keen interest in developing biomarkers and therapies to counter metastatic disease. This dissertation begins with a review on miRNAs implicated …

Novel Signaling Mechanisms Implicated In Epithelial Mesenchymal Transition And Metastasis Of Human Cancers, Minsoon Kim

Open Access Dissertations

Distant metastases are the leading cause of breast cancer related death. It is important to understand how the metastatic process is regulated in order to develop new therapies that would oppose metastasis and improve cancer outcome. Initiation of metastasis requires cell invasion and escape from the primary tumor into the vasculature followed by colonization of secondary sites. Tumor invasion and intravasation are enabled by the epithelial mesenchymal transition (EMT), a process in which epithelial cells lose polarity and intracellular adhesion and acquire motility and invasiveness. This thesis work has revealed novel mechanisms whereby cancer metastasis is regulated via induction of …