Life Sciences Commons^™

Targeting Estrogen Receptor Negative Breast Cancer Cells Using Diarylthiourea Analogs Of Sheta2, Hongye Zou

Dissertations, Masters Theses, Capstones, and Culminating Projects

Abstract will available after document embargo ends.

Immunotherapeutic Strategies To Reverse Tumor Associated Immunosuppression In Breast Cancer, Sruthi Ravindranathan

Graduate Theses and Dissertations

Heterogenous cancers such as breast carcinoma, would highly benefit from personalized vaccine approaches such as autologous tumor cell vaccines (ATCVs). By using cancer cells that are isolated from self, this approach has the potential to generate a polyclonal immune response against tumor antigens, that are specific to the individual. However, so far, ATCVs against breast cancers have not had any clinical success due to the poor immunogenicity of the malignant cells.

In this study, for the first time, we determined tumor derived G-CSF to play a major role in affecting immune response against breast cancer ATCVs. By using CRISPR/Cas9 genome …

The Rodent Parvovirus H-1 And Its Potential In Combination With Tien Hsien Liquid As A Treatment For Breast Cancer, Hayley I. Spires

Selected Honors Theses

Breast cancer is responsible for 12% of cancer diagnoses each year, and it is the leading cause of cancer-related mortality in women worldwide. Current treatments have provided some success in combatting the disease but are not considered a final solution. The framework for how researchers approach cancer has continued to change, and this includes the introduction of oncolytic viruses as novel therapeutics for cancer. The rodent parvovirus H-1 has shown strong potential in clinical and subclinical trials, but its S phase dependency limits its usefulness against cancer stem cell populations. Tien Hsien Liquid is commerically available, nontoxic, and has shown …

Investigating The Roles Of Δnp63 As A Suppressor Of Migration, Invasion, And Metastasis, Ramon E. Flores Gonzalez

Dissertations & Theses (Open Access)

Cancer is one of the leading causes of death and disease in the world. Considerable resources are spent to study and understand cancer, with the hope of developing new treatments and eventually cures that will help millions of people. Efforts to understand cancer are hindered by its inherent complexity and instability. Nonetheless, understanding the basics of tumor development and progression are the key to focused on studying the role of ΔNp63 in cancer, a p53 family member known to be involved in epithelial development, microRNA biogenesis, and stem cell maintenance. Using the strength of in vivo mouse models, we found …

The Effect Of Manganese (Mn) On Cell Proliferation And Migration In The Michigan Cancer Foundation-7 (Mcf-7) Human Breast Cancer Cell Line In Vitro, Justin Lloyd Wendel

Theses and Dissertations

Manganese (Mn) is a common environmental element necessary for mammalian physiological processes. However, dietary excess or deficiency can lead to detrimental health effects. Therefore, I investigated the effect Mn has on breast cancer progression in vitro. Utilizing MCF-7 breast cancer cells an MTT assay was performed to identify proliferative potential. After 5 days, results showed 100 nM manganese chloride (MnCl2) had a significant (p<0.01) increase in cell number over control. Using a scratch wound-healing assay, 100 nM MnCl2 was found to increase cellular motility as well as induce a possible change in morphology and cytoskeletal organization. Given Mn was shown to localize in the mitochondrial, we investigated Mn-induced ROS expression. 500 nM Mn significantly decreased (p<0.05) ROS levels. Collectively, I provide evidence that Mn may potentially drive less aggressive cancer cells towards a more invasive phenotype.

Role Of Cell Type And Genetic Alterations In Driving Breast Cancer Pathogenesis, Divya Bhagirath

Theses & Dissertations

Breast cancer is the second most leading cause of death among women in the United States. Several environmental and genetic factors contribute to the pathogenesis of the disease. It is classified into different subtypes based on expression of certain markers as well as that of set of genes that define the disease progression and associated mortality. Identification of various subtypes namely: Luminal-like (Luminal-A, Luminal-B), ErbB2 over-expressing, Basal-like and Claudin low types, showed an association of survival outcomes with that of the corresponding gene expression signatures, thus paving a way for therapeutic intervention. It further emphasizes the importance of nature of …

Role Of Ecdysoneless In Erbb2/Her2 Mediated Breast Oncogenesis, Shalis A. Ammons

Theses & Dissertations

Breast cancer is the second leading cause of cancer related deaths in women in the United States. The human Epidermal Growth Factor 2 (ErbB2) gene amplification and/or receptor overexpression subtype of breast cancer accounts for 25% of all breast cancers. A crucial regulator of the ErbB2 signaling pathway is the heat shock protein 90 (Hsp90) and its interacting protein complex. One such complex is the R2TP/Prefoldin-like complex that is composed of four proteins, RUVBL1, RUVBL2, PIH1D1, and RPAP3 and seven prefoldin-like proteins. This complex has been shown to be involved in telomere elongation, ribosome biogenesis, protein stability; etc. We and …

Restriction Enzyme Generated Next-Generation Sequencing Libraries And Genetic Risk Modifiers Of Brca1 Mutation Carriers, Bradley Downs

Theses & Dissertations

Next-generation sequencing (NGS) is a high throughput technique used to sequence large amounts of DNA in a short amount of time. However, a limitation to NGS is that the generated data is in a single consensus sequence without distinguishing between variants on homologous chromosomes. Separating or phasing the variants from the maternal and paternal chromosomes can provide information about the genetic origin of disease and information about how DNA nucleotide alterations interact in cis. This dissertation explores a new technical method of using restriction enzymes during NGS library preparation and its ability to increase the amount of phasing information that …

The Role Of Ada3 Overexpression In Proliferation Through Enhancing Myc Expression, Nicolas I. Griffin

Theses & Dissertations

Breast cancer is a heterogeneous disease that is the second leading cause of cancer related deaths in women. Cancer is defined as abnormally heightened proliferation. In order for gene transcription and eventual translation to occur to drive the cell cycle to generate more cells, DNA must be uncoiled from nucleosomes by histone acetylation complexes. One of the key evolutionarily conserved components of these HAT complexes is alteration/deficiency in activation 3 (ADA3). In addition to the role in histone acetylation, this protein also functions as a coactivator for nuclear hormone receptors. Recent findings indicated that nuclear Ada3 correlates with ER+ breast …

Rerouting Pre-Existing Host Vaccine-Induced Immunity Towards Breast Cancer, Bharat Kumar Reddy Chaganty

Dissertations & Theses (Open Access)

For decades, investigators have attempted to activate the immune system to prevent cancer metastasis or recurrence; however, owing to host immune tolerance to cancer antigens and the immunosuppressive environment at tumor sites, many such attempts have failed. The recent success of anti-CTLA4, PD-L1 and PD-1 antibodies targeting immune checkpoint pathways and HPV vaccines has renewed hope that patient survival can be increased through enhancing T-cell responses. We propose to test a novel approach that may bypass host immune tolerance to cancer cells. We hypothesize that host T-cell immunity acquired through vaccination against or natural infection with infectious diseases—e.g., influenza—can be …

The Role Of Amp-Activated Protein Kinase (Ampk) In Tumorigenesis, Fei Han

Dissertations & Theses (Open Access)

AMPK plays a central role in controlling cellular and whole body energy level. Increasing studies have also discovered the diverse function of AMPK in cancer, such as autophagy and mitochondria biogenesis. However, how AMPK promotes cancer progression is still not clear. Here, we show that AMPK is essential for EGF-induced Akt activation, Glut1 expression, and glucose uptake. AMPK is also required for various stresses induced Akt activation and promote cell survival, including hypoxia and glucose deprivation. In addition, we found glucose deprivation-induced VEGF expression and secretion is also depend on AMPK, which may contribute to angiogenesis of surrounding endothelial cell …

Trim24 Orchestrates Metabolic Reprogramming And Emt In Breast Cancer, Kaushik Thakkar

Dissertations & Theses (Open Access)

In this dissertation, I report the oncogenic functions of an epigenetic regulator Tripartite Motif Protein 24 (TRIM24) coupled with metabolic reprogramming and epithelial mesenchymal transition (EMT) in breast cancer. TRIM24 was first established by our laboratory as a previously unknown negative regulator of p53 via its RING domain, as a co-regulator of nuclear receptors and a PHD/Bromodomain reader of specific histone modifications. TRIM24 expression correlates with poor prognosis of breast cancer, but the mechanisms of TRIM24-mediated oncogenesis are unknown. In the first part of my thesis, I found that TRIM24 is aberrantly expressed in early stages of breast cancer progression. …

Expression Of Genes For Peptide/Protein Hormones And Their Cognate Receptors In Breast Carcinomas As Biomarkers Predicting Risk Of Recurrence., Michael Wesley Daniels

Electronic Theses and Dissertations

Certain hormones and/or receptors influencing normal cellular pathways were detected in breast cancers. The hypothesis is that gene subsets predict risk of breast carcinoma recurrence in patients with primary disease. Gene expression of 55 hormones and 73 receptors were determined by microarray with LCM-procured carcinoma cells of 247 de-identified biopsies. Univariate and multivariate Cox regressions were determined using expression levels of each hormone/receptor gene, individually or as a pair. Significant genes derived for each subset were analyzed to predict risk of cancer recurrence with 1000 LASSO training/test sets. A 14-gene molecular signature was identified for predicting clinical outcome without regard …

14-3-3Ζ Regulation Of Metastasis Through Mediation Of Liprin-Α And Liprin-Β, Rachel Hynes

Theses and Dissertations

Cancer is a set of varied and diverse diseases that share common characteristics, such as active proliferation, increased replicative potential, and tissue invasion or metastasis. One protein, 14-3-3ζ, is shown to be upregulated in a number of different cancers and also correlates with poor patient prognosis, recurrence, and mortality. This protein comes from a family of adapter proteins known for their scaffolding ability, pro- and anti-oncogenic capabilities, and affinity for phosphorylated substrates. It has been shown previously to participate in cancer progression, subversion of apoptosis, and to increase chemoresistance. Herein we will discuss the ability of 14-3-3ζ to promote distant-site …

Identification And Characterization Of Serum Biomarkers Associated With Breast Cancer Progression, Adhari Abdullah Alzaabi

Theses and Dissertations

Despite the recognized advances in the treatment of breast cancer, it still accounts for 15% of all cancer-related deaths. 90% of breast cancer deaths are due to unpredicted metastasis. There is neither successful treatment for metastatic patients nor a specific test to predict or detect secondary lesions. Patients with primary tumor will be either over-treated with cytotoxic side effects or under-treated and risk recurrence. This necessitates the need for personalized treatment, which is hard to offer for such heterogeneous disease. Obstacles in treating breast cancer metastasis are mainly due to the gaps exist in the understanding of the molecular mechanism …

Time To Diagnosis Of Second Primary Cancers Among Patients With Breast Cancer, Edward Okezie Irobi

Walden Dissertations and Doctoral Studies

Many breast cancer diagnoses and second cancers are associated with BRCA gene mutations. Early detection of cancer is necessary to improve health outcomes, particularly with second cancers. Little is known about the influence of risk factors on time to diagnosis of second primary cancers after diagnosis with BRCA-related breast cancer. The purpose of this cohort study was to examine the risk of diagnosis of second primary cancers among women diagnosed with breast cancer after adjusting for BRCA status, age, and ethnicity. The study was guided by the empirical evidence supporting the mechanism of action in the mutation of BRCA leading …