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Protective Benefits Of Hydrogen Sulfide Treatment During Renal Transplantation, Ian Lobb Aug 2016

Protective Benefits Of Hydrogen Sulfide Treatment During Renal Transplantation, Ian Lobb

Electronic Thesis and Dissertation Repository

Ischemia/reperfusion injury (IRI) is inherent to renal transplantation (RTx) and is initiated when blood supply is necessarily removed during organ procurement (ischemia) and subsequently restored upon engraftment (reperfusion). During renal ischemia, ATP depletion causes tubular epithelial cell (TEC) injury and subsequent release of pro-inflammatory mediators. Upon reperfusion, influx of O2 causes reactive oxygen species (ROS) production and infiltration of innate immune cells which release damaging ROS and proteases. Prolonged periods of IRI are associated with increased risk of delayed graft function (DGF) and decreased long-term graft survival. The endogenously produced gasotransmitter, hydrogen sulfide (H2S), has recently been …


The Resolution Phase Of Nk Cell Proliferation And Ifn Production Following Viral Infection Are Highly Regulated Processes., Leslie Abigail Fogel May 2016

The Resolution Phase Of Nk Cell Proliferation And Ifn Production Following Viral Infection Are Highly Regulated Processes., Leslie Abigail Fogel

Arts & Sciences Electronic Theses and Dissertations

In response to MCMV infection, NK cells undergo three distinct phases of proliferation: the non-specific phase mediated by pro-proliferative cytokines; the specific phase mediated by recognition of an MCMV-encoded protein by an NK cell activating receptor, Ly49H; and the resolution phase, whose mechanism is unknown. MCMV infection of RAG mice, which lack all adaptive immune cells, results in prolonged proliferation of NK cells despite similar viral titers compared to wildtype mice. Interestingly, there are different kinetics for Ly49H+ and Ly49H- NK cells. We have identified several additional markers that may distinguish NK cells that have been specifically activated through their …


Overcoming Treatment Resistance In Heterogeneous Tumors, Nikhil Hebbar Jan 2016

Overcoming Treatment Resistance In Heterogeneous Tumors, Nikhil Hebbar

Theses and Dissertations--Toxicology and Cancer Biology

Most primary tumors are heterogeneous and are often composed of therapy-sensitive and emerging therapy-resistant cancer cells. Rather unexpectedly, treatment of therapy-sensitive tumor cells in heterogeneous tumor microenvironments resulted in apoptosis of the therapy-resistant cancer cells. We identified a novel Par-4 amino-terminal fragment (PAF, which includes amino acids 1-131 of Par-4) that is produced and released by therapy-sensitive cancer cells following therapy-induced caspase-dependent cleavage of the tumor suppressor Par-4. PAF caused paracrine apoptosis in therapy-resistant cancer cells. Unlike Par-4-inducible apoptosis, which is dependent on the cell surface GRP78 receptor, PAF produced cancer-selective apoptosis independent of cell surface GRP78 function. Par-4 contains …


Tumor-Specific Cell Death Induction By Noxa Overexpression For Head And Neck Squamous Cell Carcinoma (Hnscc) Treatment, Nicolas T. Maxim Mr. Jan 2016

Tumor-Specific Cell Death Induction By Noxa Overexpression For Head And Neck Squamous Cell Carcinoma (Hnscc) Treatment, Nicolas T. Maxim Mr.

Theses and Dissertations

The primary focus of this research is the mechanisms of cell death in head and neck squamous cell carcinoma (HNSCC) treatment. These cancers typically originate in squamous cells that line the moist mucosal surfaces of head and neck. HNSCC is commonly treated with a platinum based agent, cisplatin. While the drug does offer strong antitumor effects, its prolonged use often results in tumor-acquired resistance, which limits treatment effectiveness. We have shown that cisplatin treatment induces the expression of a pro-apoptotic BCL-2 family member Noxa, which then initiates caspase- dependent apoptosis through its binding and sequestration of pro-survival protein MCL-1 for …