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GSBS Dissertations and Theses

Apoptosis

Diseases

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Full-Text Articles in Medicine and Health Sciences

Innate Immunity As Mediator Of Cell Death And Inflammation In Alcoholic Liver Disease, Arvin Iracheta-Vellve Nov 2017

Innate Immunity As Mediator Of Cell Death And Inflammation In Alcoholic Liver Disease, Arvin Iracheta-Vellve

GSBS Dissertations and Theses

Central driving forces in the pathogenesis of liver disease are hepatocyte death and immune cell-driven inflammation. The interplay between outcomes, stemming from these two major cell types, is present from the earliest ethanol exposure, and are both determinants in advanced stages of liver disease particularly in alcoholic liver disease (ALD). The complexities associated with advanced ALD are many and therapies are limited. Due to the liver’s role in ethanol metabolism and filtering gut-derived products, it is becoming increasingly clear that innate immunity plays a central role in triggering activation of cell death and inflammatory pathways in ALD. We identified ...


Exploiting Dna Repair And Er Stress Response Pathways To Induce Apoptosis In Glioblastoma Multiforme: A Dissertation, Jessica L. Weatherbee Aug 2016

Exploiting Dna Repair And Er Stress Response Pathways To Induce Apoptosis In Glioblastoma Multiforme: A Dissertation, Jessica L. Weatherbee

GSBS Dissertations and Theses

Glioblastoma multiforme (GBM) is a deadly grade IV brain tumor characterized by a heterogeneous population of cells that are drug resistant, aggressive, and infiltrative. The current standard of care, which has not changed in over a decade, only provides GBM patients with 12-14 months survival post diagnosis. We asked if the addition of a novel endoplasmic reticulum (ER) stress inducing agent, JLK1486, to the standard chemotherapy, temozolomide (TMZ), which induces DNA double strand breaks (DSBs), would enhance TMZ’s efficacy. Because GBMs rely on the ER to mitigate their hypoxic environment and DNA repair to fix TMZ induced DSBs, we ...


Txnip Is A Mediator Of Er Stress-Induced Β-Cell Inflammation And Apoptosis: A Dissertation, Christine M. Oslowski May 2012

Txnip Is A Mediator Of Er Stress-Induced Β-Cell Inflammation And Apoptosis: A Dissertation, Christine M. Oslowski

GSBS Dissertations and Theses

Diabetes mellitus is a group of metabolic disorders characterized by hyperglycemia. The pathogenesis of these diseases involves β-cell dysfunction and death. The primary function of β-cells is to tightly regulate the secretion, production, and storage of insulin in response to blood glucose levels. In order to manage insulin biosynthesis, β-cells have an elaborate endoplasmic reticulum (ER).

The ER is an essential organelle for the proper processing and folding of proteins such as proinsulin. Proteins fold properly when the ER protein load balances with the ER folding capacity that handles this load. Disruption of this ER homeostasis by genetic and environmental ...


Regulation Of Cancer Cell Survival Mediated By Endogenous Tumor Suppression: A Dissertation, Minakshi Guha Jul 2009

Regulation Of Cancer Cell Survival Mediated By Endogenous Tumor Suppression: A Dissertation, Minakshi Guha

GSBS Dissertations and Theses

Cancer is the second leading cause of death among men and women after heart disease. Though our knowledge associated with the complexities of the cancer network has significantly improved over the past several decades, we have only recently started to get a more complete molecular understanding of the disease. To better comprehend signaling pathways that prevent disease development, we focused our efforts on investigating endogenous tumor suppression networks in controlling effectors of cancer cell survival and proliferation. Survivin is one such effector molecule that controls both cell proliferation and survival. In order to identify how this protein is overexpressed in ...


Defining The Role Of Ctbp2 In P53-Independent Tumor Suppressor Function Of Arf: A Dissertation, Ramesh C. Kovi Jun 2009

Defining The Role Of Ctbp2 In P53-Independent Tumor Suppressor Function Of Arf: A Dissertation, Ramesh C. Kovi

GSBS Dissertations and Theses

ARF, a potent tumor suppressor, positively regulates p53 by antagonizing MDM2, a negative regulator of p53, which in turn, results in either apoptosis or cell cycle arrest. ARF also suppresses the proliferation of cells lacking p53, and loss of ARF in p53-null mice, compared with ARF-null or p53-null mice, results in a broadened tumor spectrum and decreased tumor latency. This evidence suggests that ARF exerts both p53-dependent and p53-independent tumor suppressor activity. However, the molecular pathway and mechanism of ARF’s p53-independent tumor suppressor activity is not understood.

The antiapoptotic, metabolically regulated, transcriptional corepressor C-terminal binding protein 2 (CtBP2) has ...


Dna Damage-Induced Apoptosis In The Presence And Absence Of The Tumor Suppressor P53: A Dissertation, Laura Michelle Mcnamee Oct 2008

Dna Damage-Induced Apoptosis In The Presence And Absence Of The Tumor Suppressor P53: A Dissertation, Laura Michelle Mcnamee

GSBS Dissertations and Theses

A key regulator of DNA damage-induced apoptosis is the tumor suppressor gene, p53. p53 is a transcription factor that upregulates genes involved in cell cycle arrest, apoptosis, and senescence. How p53 decides to activate one of these responses in response to DNA damage is largely unanswered. Many have hypothesized it is due to interaction with various signaling pathways and post-translational modification. The p53 tumor suppressor can be modified by SUMO-1 in mammalian cells, but the functional consequences of this modification are unclear. Conjugation to SUMO is a reversible post-translational modification that regulates several transcription factors involved in cell proliferation, differentiation ...


Functional Analysis Of Ing1 And Ing4 In Cell Growth And Tumorigenesis: A Dissertation, Andrew H. Coles May 2008

Functional Analysis Of Ing1 And Ing4 In Cell Growth And Tumorigenesis: A Dissertation, Andrew H. Coles

GSBS Dissertations and Theses

The five member Inhibitor of Growth (ING) gene family has been proposed to participate in the regulation of cell growth, DNA repair, inflammation, chromatin remodeling, and tumor suppression. All ING proteins contain a PHD motif implicated in binding to methylated histones and are components of large chromatin remodeling complexes containing histone acetyltransferase (HAT) and histone deacetylase (HDAC) enzymes, suggesting a role for ING proteins in regulating gene transcription. Additionally, forced overexpression studies performed in vitro have indicated that several ING proteins can interact with the p53 tumor suppressor protein and/or the NF-кB protein complex. Since these two proteins play ...


Attrition Of Cd8 T Cells During The Early Stages Of Viral Infections: A Dissertation, Kapil Bahl Jan 2008

Attrition Of Cd8 T Cells During The Early Stages Of Viral Infections: A Dissertation, Kapil Bahl

GSBS Dissertations and Theses

Profound lymphopenia has been observed during many acute viral infections, and our laboratory has previously documented a type 1 IFN-dependent loss of most memory (CD44hi) and some naïve (CD44lo) CD8 T cells immediately preceding the development of the antiviral T cell response at days 2-4 following lymphocytic choriomeningitis virus (LCMV) infection. In this thesis, I will examine additional mechanisms involved in the early attrition of CD8 T cells and evaluate whether antigen-specific and non-specific CD8 T cells are equally susceptible. Lastly, I will examine whether the early attrition of CD8 T cells contributes to the generation of an ...


Dissecting The Mechanism For The Selective Induction Of Apoptosis In Transformed Cells By Cav Apoptin: A Dissertation, Destin W. Heilman Mar 2006

Dissecting The Mechanism For The Selective Induction Of Apoptosis In Transformed Cells By Cav Apoptin: A Dissertation, Destin W. Heilman

GSBS Dissertations and Theses

Most existing chemotherapeutics lack adequate specificity for transformed cells and therefore have high rates of collateral damage to normal tissue. Moreover, such therapies often depend on p53 to induce cell death and are ineffective on the large number of human cancers that have lost p53 function. The discovery of novel p53-independent cancer therapies is therefore of significant interest. The Chicken Anemia Virus protein Apoptin selectively induces apoptosis in transformed cells in a p53-independent manner while leaving normal primary cells unaffected. This selectivity is thought to be largely due to cell type-specific localization: in primary cells Apoptin is cytoplasmic, whereas in ...


Pathways Linking Deregulated Proliferation To Apoptosis: A Dissertation, Harry A. Rogoff Apr 2004

Pathways Linking Deregulated Proliferation To Apoptosis: A Dissertation, Harry A. Rogoff

GSBS Dissertations and Theses

Proper regulation of cellular proliferation is critical for normal development and cancer prevention. Most, if not all, cancers contain mutations in the Rb/E2F pathway, which controls cellular proliferation. Inactivation of the retinoblastoma protein (Rb) can occur through Rb loss, mutation, or inactivation by cellular or viral oncoproteins leading to unrestrained proliferation. This occurs primarily by de-repression and activation of the E2F transcription factors, which promote the transition of cells from the G1to S phase of the cell cycle. In order to protect against loss of growth control, the p53 tumor suppressor is able to induce programmed cell ...