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Full-Text Articles in Diseases

Stat5a Regulation By Serine Phosphorylation In Breast Cancer, Alicia E. Woock Jan 2021

Stat5a Regulation By Serine Phosphorylation In Breast Cancer, Alicia E. Woock

Theses and Dissertations

The neuroendocrine hormone prolactin (PRL) and its cognate receptor (PRLr) have been implicated in the pathogenesis of breast cancer. PRL signaling relies on activating kinases such as the tyrosine kinase Jak2 and serine/threonine kinases ERK1/2, NEK3, PI3K, and AKT. In the canonical pathway of PRL signaling, JAK2 phosphorylates the transcription factor STAT5a at tyrosine residue 694 (pY694-STAT5a), preceding STAT5a nuclear translocation and transcriptional activity. However, STAT5a exists with functional duality as a transcription factor, having both pro-differentiative and pro-proliferative target genes. Other STAT family members (STATs 1, 3, and 6) have been shown to have transcriptional activity in the un-tyrosine-phosphorylated …


From Bedside To Bench: Use Of Patient-Derived Xenograft Models To Develop Novel Therapeutic Strategies For Triple-Negative Breast Cancer, Tia H. Turner Jan 2020

From Bedside To Bench: Use Of Patient-Derived Xenograft Models To Develop Novel Therapeutic Strategies For Triple-Negative Breast Cancer, Tia H. Turner

Theses and Dissertations

Triple-negative breast cancer (TNBC) is a clinically aggressive disease that is associated with bleak outcomes due to its metastatic propensity, frequent failure to respond to chemotherapy, and lack of alternative treatment options. Despite decades of major translational research efforts, there has been very little success thus far in the development of effective targeted therapies for this disease. It is imperative to develop novel therapeutic strategies to improve patient outcomes, as well as minimize the toxicity associated with standard-of-care chemotherapeutics. Given that metastatic disease accounts for the vast majority of TNBC-related deaths, a better understanding of therapeutic responses within common sites …


The Role Of Syndecan-1 And Extracellular Vesicles In Breast Cancer Brain Metastasis, Megan R. Sayyad Jan 2019

The Role Of Syndecan-1 And Extracellular Vesicles In Breast Cancer Brain Metastasis, Megan R. Sayyad

Theses and Dissertations

Breast cancer metastasizes to the brain in 15-30% of all breast cancer cases, and metastasis is the predominant cause of breast cancer-related deaths. Patients with HER2-enriched and triple-negative breast cancers (TNBCs) are more likely to develop brain metastases. While targeted therapies exist for HER2-enriched breast cancers, there are no effective treatments for TNBCs. Thus, a greater understanding of how these cancers spread to the brain is critical. In order to spread to the brain, disseminated breast cancer cells must overcome 2 major steps—crossing the blood-brain barrier (BBB) and survival and successful colonization of the distinctive and mostly cellular brain environment. …


Sildenafil And Celecoxib Interact To Kill Breast Cancer Cells, Brittany Binion Jan 2014

Sildenafil And Celecoxib Interact To Kill Breast Cancer Cells, Brittany Binion

Theses and Dissertations

Breast cancer is the second most commonly diagnosed cancer among American women and is responsible for the second highest number of cancer-related deaths. Targeted therapeutic agents sildenafil, a phosphodiesterase type 5 inhibitor, and celecoxib, a cyclooxygenase-2 inhibitor, have been used individually in conjunction with other chemotherapeutic agents to enhance cell killing in a variety of cancers. Sildenafil when combined with traditional chemotherapeutic drugs, such as the taxanes and anthracyclines, or celecoxib combined with traditional hormone therapies have been used to increase cytotoxicity and cell killing. The data presented here demonstrates that the novel combination of sildenafil and celecoxib work together …