Biochemistry Commons^™

Runx1 Loss Leads To An Epithelial To Mesenchymal Transition In Breast Cancer By Regulating Target Gene Expression., Dorcas Lohese

Graduate College Dissertations and Theses

Breast cancer is the second leading cause of cancer death among women in the United States. Due to the various advancements in treatment, the five-year survival rate is greater than 90% among women with non-metastatic breast cancer. However, among patients with metastatic breast cancer, the five-year survival rate quickly drops to 22%. Recognizing early signs of metastasis is essential for targeting cancer before it disseminates. The epithelial-to-mesenchymal transition (EMT) is hypothesized to be a vital process for large-scale cell movement by disrupting cell-cell adhesion, allowing metastatic breast cancer cells to become more migratory. The progression of breast cancer EMT involves …

Exploring The Mechanisms Of Pkg1-Α Activation By Synthetic Peptides, Connor Cronin

Graduate College Dissertations and Theses

Cyclic GMP-dependent protein kinases (PKG’s) are essential signaling macromolecules which play a pivotal role in vascular physiology and smooth muscle tone regulation. As principle downstream effectors of the secondary messenger cyclic 3’, 5’-guanosine-monophosphate (cGMP), PKG isoforms are expressed in high levels in all types of smooth muscle cells. The broad range of cellular functions effected by PKG include platelet aggregation, hypertrophy, apoptosis, neuronal plasticity, gene expression, differentiation, vasorelaxation, vascular remodeling, calcium homeostasis, and cardiac function. Recently, a newly characterized helical switch domain within the alpha isoform of PKG (PKG1-α) has led to the development of S1.1, a novel cGMP-independent peptide …

Designer Biologics Composed Of Hepatocyte Growth Factor, Fibroblast Growth Factor 2 And Immunoglobulin G For Treatment Of Acute Myocardial Infarction, Benjamin Liebman

Graduate College Dissertations and Theses

ABSTRACT Coronary artery disease leading to myocardial infarction (a.k.a. MI, heart attack) is one of the leading causes of death globally. Each year an estimated 605,000 Americans suffer a heart attack, which equates to one MI every 40 seconds. As such, MI represents one of the largest health burdens to society. The current standard of care is revascularization therapy achieved by fibrinolytics and Percutaneous Coronary Intervention (PCI); both of which re-open occluded proximal arteries to restore blood flow to the affected areas. Despite revascularization therapy, 30-50% of patients exhibit a form of reperfusion injury termed “no/low-reflow” in which the blood …

Tsrna Involvement In Promoting Breast Cancer Phenotypes, Stephanie Scalia

Graduate College Dissertations and Theses

The overall 5-year survival rate for woman diagnosed with breast cancer has increased significantly over the last 20 years. However, prognosis for women with stage IV, metastatic disease remains very poor. Women diagnosed with stage 0-III breast cancer have above an 85% chance of survival over a 5-year period while women diagnosed with stage IV breast cancer have a 5-year survival of less than 30%. A better understanding of the molecular mechanisms driving aggressive breast cancer is essential for the potential discovery of more targeted therapies to increase the survival rates for women diagnosed with stage IV breast cancer.

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Changes In Threonyl-Trna Synthetase Expression And Secretion In Response To Endoplasmic Reticulum Stress By Monensin In Ovarian Cancer Cells, Jared Louis Hammer

Graduate College Dissertations and Theses

Aminoacyl-tRNA synthetases (ARS) are a family of enzymes that catalyze the charging of amino acids to their cognate tRNA in an aminoacylation reaction. Many members of this family have been found to have secondary functions independent of their primary aminoacylation function. Threonyl-tRNA synthetase (TARS), the ARS responsible for charging tRNA with threonine, is secreted from endothelial cells in response to both vascular endothelial growth factor (VEGF) and tumor necrosis factor-α (TNF-α), and stimulates angiogenesis and cell migration. Here we show a novel experimental approach for studying TARS secretion, and for observing the role of intracellular TARS in the endoplasmic reticulum …

Characterization Of A Non-Canonical Function For Threonyl-Trna Synthetase In Angiogenesis, Adam Christopher Mirando

Graduate College Dissertations and Theses

In addition to its canonical role in aminoacylation, threonyl-tRNA synthetase (TARS) possesses pro-angiogenic activity that is susceptible to the TARS-specific antibiotic borrelidin. However, the therapeutic benefit of borrelidin is offset by its strong toxicity to living cells. The removal of a single methylene group from the parent borrelidin generates BC194, a modified compound with significantly reduced toxicity but comparable anti-angiogenic potential. Biochemical analyses revealed that the difference in toxicities was due to borrelidin's stimulation of amino acid starvation at ten-fold lower concentrations than BC194. However, both compounds were found to inhibit in vitro and in vivo models of angiogenesis at …