Life Sciences Commons^™

A Quantitative Visualization Tool For The Assessment Of Mammographic Risky Dense Tissue Types, Margaret R. Mccarthy

Electronic Theses and Dissertations

Breast cancer is the second most occurring cancer type and is ranked fifth in terms of mortality. X-ray mammography is the most common methodology of breast imaging and can show radiographic signs of cancer, such as masses and calcifcations. From these mammograms, radiologists can also assess breast density, which is a known cancer risk factor. However, since not all dense tissue is cancer-prone, we hypothesize that dense tissue can be segregated into healthy vs. risky subtypes. We propose that risky dense tissue is associated with tissue microenvironment disorganization, which can be quantified via a computational characterization of the whole breast …

Epitranscriptomic Regulation In Breast Cancer And Pcb-Induced Liver Disease., Belinda Petri

Electronic Theses and Dissertations

Post-transcriptional RNA modifications including N6-methyladenosine (m6A) regulate mRNA stability, splicing, and translation. My research examined m6A in two disease models: breast cancer (BCa) and non-alcoholic fatty liver disease (NAFLD). Acquired resistance to endocrine therapies (ET) develops in approximately 20% of BCa patients with estrogen receptor α positive (ER+) tumors following treatment. The mechanisms by which tumor cells evade ET are not completely understood. Using a cell line model, we investigated the role of an m6A reader protein, HNRNPA2B1 (A2B1) that is upregulated in ET-resistant ER+ BCa cells. Stable overexpression of A2B1 in ET-sensitive MCF-7 cells (MCF-7-A2B1), results in ET resistance, …

The Influence Of Administrative Timing In Triple-Negative Breast Cancer Treatments, Emily Mailloux

Electronic Theses and Dissertations

Breast cancer accounts for 25% of all cancers in Canadian women, and 15-20% of these are triple-negative breast cancers (TNBC), which have a poorer prognosis than other breast cancer subtypes. TNBC lacks expression of the estrogen receptor, progesterone receptor, and the human epidermal growth factor receptor 2 (HER2), which are common therapeutic targets in breast cancer. Due to the lack of target therapy, generalized chemotherapy treatments are used instead. The standard of care for treatment of TNBC instead consists of doxorubicin (A), cyclophosphamide (C) paclitaxel (T), and carboplatin (Carbo), that target various aspects of the cell cycle to induce cell …

Bayesian Methods For Graphical Models With Neighborhood Selection., Sagnik Bhadury

Electronic Theses and Dissertations

Graphical models determine associations between variables through the notion of conditional independence. Gaussian graphical models are a widely used class of such models, where the relationships are formalized by non-null entries of the precision matrix. However, in high-dimensional cases, covariance estimates are typically unstable. Moreover, it is natural to expect only a few significant associations to be present in many realistic applications. This necessitates the injection of sparsity techniques into the estimation method. Classical frequentist methods, like GLASSO, use penalization techniques for this purpose. Fully Bayesian methods, on the contrary, are slow because they require iteratively sampling over a quadratic …

Deep Learning Applications In Medical Bioinformatics, Ziad Omar

Electronic Theses and Dissertations

After a patient’s breast cancer diagnosis, identifying breast cancer lymph node metastases is one of the most important and critical factor that is directly related to the patient’s survival. The traditional way to examine the existence of cancer cells in the breast lymph nodes is through a lymph node procedure, biopsy. The procedure process is time-consuming for the patient and the provider, costly, and lacks accuracy as not every lymph node is examined. The intent of this study is to develop an artificial neural network (ANNs) that would map genetic biomarkers to breast lymph node classes using ANNs. The neural …

The Role Of The Nkr-P1b:Clr-B Inhibitory Axis In Nk Cell-Mediated Tumour Immunosurveillance, Abd El Aziz Hendy

Electronic Theses and Dissertations

Natural killer (NK) cells are lymphocytes of the innate immune system which do not require prior priming to target infected or altered-self cells, such as tumour cells. The basic functions of NK cells include cytotoxicity and cytokine production. These cells possess numerous activating and inhibitory receptors which regulate their function based on a signalling balance. In mice, NK cells possess NKR-P1B inhibitory receptors which recognize the C-type lectin-related protein-b (Clr-b) ligand. This ligand is present on healthy self cells and may be used by cancer cells to evade NK cell effector functions. The disruption of the NKR-P1B:Clr-b axis has been …

Deciphering The Role Of Human Arylamine N-Acetyltransferase 1 (Nat1) In Breast Cancer Cell Metabolism Using A Systems Biology Approach., Samantha Marie Carlisle

Electronic Theses and Dissertations

Background: Human arylamine N-acetyltransferase 1 (NAT1) is a phase II xenobiotic metabolizing enzyme found in almost all tissues. NAT1 can additionally hydrolyze acetyl-coenzyme A (acetyl-CoA) in the absence of an arylamine substrate. NAT1 expression varies inter-individually and is elevated in several cancers including estrogen receptor positive (ER+) breast cancers. Additionally, multiple studies have shown the knockdown of NAT1, by both small molecule inhibition and siRNA methods, in breast cancer cells leads to decreased invasive ability and proliferation and decreased anchorage-independent colony formation. However, the exact mechanism by which NAT1 expression affects cancer risk and progression remains unclear. Additionally, consequences …

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 …

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 …

The Ras Effector Nore1a Forms A Tumor Suppressor Complex With Brca1., Nicholas C Nelson

Electronic Theses and Dissertations

Ras proteins function as molecular signaling switches that can stimulate multiple mitogenic pathways in response to extracellular signaling. Oncogenic activation of Ras by structural mutation is a highly transforming event in ~1/3 of human cancers. However, aberrant Ras activation can also promote oncogene-induced senescence. This Ras-induced irreversible growth arrest is a physiological process that acts as a barrier to malignancy. The mechanisms by which Ras drives senescence and how this process is bypassed during Ras-driven transformation remains poorly understood.

Although mutations in the RAS gene are extremely rare in human breast cancer, the Ras signaling pathway is constitutively activated in …

Sa-4-1bbl As A Platform To Develop Adjuvant Systems For Prophylactic And Therapeutic Vaccines., Gunes Dinc 1984-

Electronic Theses and Dissertations

Vaccines against infectious diseases are one of the most critical accomplishments in modern medicine. Despite significant progress in vaccinology, there is still a dire need for developing vaccines against various acute and chronic infections and cancer. In general, vaccines are categorized as prophylactic, given to healthy individuals to prevent disease, and therapeutic, administered to people who already have disease. As such, the nature, quality, and quantity of immune responses required for the efficacy of these two types vaccines are different. Prophylactic vaccines against infectious diseases primarily rely on the generation of neutralizing high titers of antibody for their efficacy. These …

Investigating Potential Bioactive Compounds From Rhodococcus And Their Effects On Mcf7 Breast Cancer Cells, Megan N. Crabtree

Electronic Theses and Dissertations

Many drugs used in the treatment of various cancers are derived from or influenced by compounds from nature. The soil bacterium Rhodococcus is of interest because of its identified secondary metabolic pathways and the production of novel natural antibiotics from several strains. In this study, a solid agar extraction method was used to collect compounds from strains of Rhodococcus. These bacterial compound extracts were then tested using a MTT assay in order to evaluate their effectiveness in augmenting MCF7 breast cancer cell death. The results of two way ANOVA analyses revealed 18 compound extracts from 15 strains of Rhodococcus that …

Identification Of Epithelial Stromal Interaction 1 And Epidermal Growth Factor Receptor As Novel Kruppel-Like Factor 8 Targets In Promoting Breast Cancer Progression, Tianshu Li

Electronic Theses and Dissertations

Breast cancer is the major cause of cancer death among women worldwide. Understanding the mechanisms underlying breast cancer progression remains urgent for developing effective treatment strategies to eliminate breast cancer mortality. Our recent studies have demonstrated that Krüppel-like transcriptional factor 8 (KLF8) plays a critical role for breast cancer progression. Other studies have shown that Epithelial stromal interaction 1 (EPSTI1), a recently identified stromal fibroblast-induced gene in non-invasive breast cancer cells and epidermal growth factor receptor (EGFR) are highly overexpressed in aggressively invasive breast carcinomas including triple negative breast cancers. In this thesis project, we demonstrate high co-overexpression of KLF8 …

Use Of Cerium Oxide Nanoparticles For Protection Against Radiation-Induced Cell Death, Jimmie Colon

Electronic Theses and Dissertations

The ability of engineered cerium oxide nanoparticles to confer radioprotection was examined. Rat astrocytes were treated with cerium oxide nanoparticles to a final concentration of 10 nanomolar, irradiated with a single 10 Gy dose of ionizing radiation and cell death was evaluated by propidium iodine uptake at 24 and 48 hours after radiation insult. Treatment of rat astrocytes with nanoceria resulted in an approximate 3-fold decrease in radiation induced death. These results suggest that the nanoceria are conferring protection from radiation induced cell death. Further experiments with human cells were conducted. Human normal and tumor cells (MCF-7 and CRL8798) were …