Medicine and Health Sciences Commons^™

Treatment Of Ischemia Reperfusion Injury With Rna Interference, Terry M. Zwiep

Electronic Thesis and Dissertation Repository

Ischemia reperfusion injury (IRI) occurs during transplantation and causes apoptosis and inflammation. The purpose of this research was to determine the effect of caspase-3, complement 3, and RelB gene silencing in the reduction of IRI using an in vitro model.

LLC-PK1 cells were used along with antimycin A for the in vitro IRI model. Prior to exposure to antimycin A, cells were transfected with caspase-3, C3, and RelB small interfering RNA (siRNA) alone or in combination and then analyzed.

The relative risk reduction of apoptosis in antimycin A treated cells with caspase-3 siRNA was 46.6% (p=0.019), RelB siRNA 42.8% (p=0.038), …

Supplementation With Hydrogen Sulfide Helps Mitigate The Effects Of Ischemia Reperfusion Injury In A Model Of Donation After Cardiac Death Renal Transplantation, Jaskirandeep Kaur Grewal

Electronic Thesis and Dissertation Repository

Donation after cardiac death (DCD) grafts experience prolonged ischemia reperfusion injury (IRI) leading to higher rates of delayed graft function and failure. Recent studies have reported protective effects of hydrogen sulfide (H₂S) against IRI. Our study aims at improving DCD renal graft outcomes by H₂S supplementation in an in-vivo murine model of renal transplantation (RTx) and study the underlying mechanism in an in-vitro model using porcine kidney proximal-tubular-epithelial cells (LLC-PK1). H₂S provided survival benefit, improved renal graft function and decreased renal injury in recipient rats. In our in-vitro model of LLC-PK1 cells, H_{2 …}

The Regulation And Mechanisms Of Egfr-Mediated Apoptosis In Mda-Mb-468 Cells., Nicole Marion Jackson

Electronic Theses and Dissertations

Background: The Epidermal Growth Factor Receptor (EGFR) is a 170- kilodalton transmembrane protein that belongs to the ErbB family of receptor tyrosine kinases. Upon ligand-mediated activation, the EGFR responsible for cell growth, proliferation, and tissue homeostasis in epithelial cells; however, the EGFR is overexpressed in many human malignancies including MDA-MB-468 cells, a metastatic breast epithelial cell line. Previous studies have indicated that within the MDA-MB-468 cell line, receptors at the cell surface promote cell growth when activated with Epidermal Growth Factor (EGF) ligand. Activated receptors that are internalized to the endosomes however induce apoptosis. This contrasting response at different cellular …

Rest Regulatory Circuit Controls Distinct Oncogenic Properties Of Glioblastoma Stem Cells Through Specific Micrornas, Anantha L Marisetty

Dissertations & Theses (Open Access)

Glioblastoma Multiforme (GBM) is the most common and aggressive primary malignant brain tumor in adults. With an average survival of only 12-16 months the prognosis for GBM patients remains dismal, with less than 5% of patients surviving 5 years. New mechanism-based approaches are necessary for the management of patients with GBM. Many GBM tumors are believed to be caused by self-renewing, glioblastoma-derived stem-like cells (GSCs). These GSCs are resistant to chemo- and radiation therapies, and are believed to be responsible for tumor recurrence. In a recent paper from our lab we have shown that REST, RE1-silencing transcription factor, regulates oncogenic …

Mechanisms Of Atf4-Mediated Neuronal Apoptosis, Patrick Swan

Electronic Thesis and Dissertation Repository

Abstract to be provided

Timp3 Regulation Of Macrophage Activation And Apoptosis, Michael S. Brock

Electronic Thesis and Dissertation Repository

Acute respiratory distress syndrome (ARDS) is a lung disease involving profound inflammation. Origins of persistent inflammation in select cases of ARDS are poorly understood, and we propose persistent inflammatory macrophages may be one of its mechanisms. Macrophages polarize to either promote inflammation, or suppress inflammation. Tissue inhibitor of metalloproteinases 3 (TIMP3) reduces the pro-inflammatory polarization in macrophages. Additionally, studies have shown TIMP3 promotes apoptosis, and its absence delays recovery from bleomycin-induced lung injury.

We hypothesize that TIMP3 promotes apoptosis of murine macrophages through inhibition of metalloproteinase activity and stabilization of FAS on the cell surface. Pro-inflammatory Timp3^-/- bone marrow-derived …

Targeting Autophagy In Multiple Myeloma, Yun Dai

Theses and Dissertations

Apoptosis (Type I) and autophagy (Type II) represent two major forms of programmed cell death. Numerous anticancer agents employed in standard chemotherapy or novel targeted therapy induce both apoptosis and autophagy. Of note, a cytoprotective autophagic response often counteracts apoptosis triggered by such agents, potentially contributing to drug-resistance. Mechanistically, autophagy and apoptosis share molecular regulatory mechanisms primarily governed by the Bcl-2 family proteins. However, since autophagy acts as the double-edge sword in cancer, whether autophagy should be inhibited or activated in cancer treatment remains the subject of debate. Here we report a) a novel autophagy-targeted strategy that targeting the adaptor …

The Role Of Noxa/Mcl-1 In Head And Neck Squamous Cell Carcinoma (Hnscc) Treatment, June Young Lee

Theses and Dissertations

Head and neck cancer is the sixth leading type of cancer with 90 percent of head and neck cancer arising from squamous cell lining on the epithelium of the oral and nasal cavity, pharynx, and salivary gland. Even with tremendous achievements on chemotherapeutic drugs and therapies, the long-term prognosis of patients with advanced head and neck squamous cell carcinoma (HNSCC) has shown little improvement over the last three decades. Cisplatin is one of widely used chemotherapeutic drugs for multiple

cancers, including head and neck cancer, but the prolonged use of this drug is limited by its toxicity and by the …

Rna Aptamers For Molecular Chaperones Hsp27 And Hsp90, Sathishkumar Kumar Munusamy

Legacy Theses & Dissertations (2009 - 2024)

Hsp90 and Hsp27 are members of the heat shock protein family of chaperones that perform multiple roles in cellular maintenance through protein folding and inhibition of apoptosis. They are abundantly expressed in cells and are over-expressed during conditions of stress. Hsp90 requires ATP for its chaperone function while Hsp27 self-associates into higher order oligomers enclosing its substrate. Their ability to interact with other proteins or with themselves lies at the heart of their mechanisms. The specific consequences of each of their interactions on global cellular health have not yet been fully discovered. The sheer diversity of proteins that interact with …

The Physiological Stress Response Caused By Hypoxia And Reperfusion Injury In Striped Bass (Morone Saxatilis) And Nile Tilapia (Oreochromis Niloticus), Amanda C. Reynolds

Electronic Theses and Dissertations

Approximately five million people in the United States are affected by cardiovascular related diseases yearly contributing to 300,000 annual deaths, making CVD the leading cause of mortality worldwide. It has been suggested that apoptosis (programmed cell death) contributes to the pathogenesis of cardiovascular diseases. When blood flow is reduced or cut off from the heart, usually by a thrombus, this results in oxygen deprivation (hypoxia) to the cardiomyocytes (heart cells). In response to this hypoxic stress, cardiomyocytes will undergo apoptosis. Since many species of fish can survive levels of hypoxia that would be fatal to mammals, fish are an ideal …