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GSBS Dissertations and Theses

Apoptosis

Neoplasms

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Full-Text Articles in Medicine and Health Sciences

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 ...


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 ...


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 ...