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Theses/Dissertations

2013

Cancer

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Full-Text Articles in Life Sciences

Rna Interference Targeting Glucose-Regulated-Protein 78 Induces Hepg2 Cell Apoptosis, Brittany Blackman Dec 2013

Rna Interference Targeting Glucose-Regulated-Protein 78 Induces Hepg2 Cell Apoptosis, Brittany Blackman

Seton Hall University Dissertations and Theses (ETDs)

Cancer is a complex genetic disease that is driven by genetic mutations resulting in chronic, inappropriate cell proliferation. Many current cancer therapies lack specificity towards tumor tissues, ultimately leading to adverse side effects and limited clinical efficacy. Recently, selective cancer cell therapy has examined a well-characterized cell surface marker that is preferentially expressed on tumor cells. The over-expression of an endoplasmic reticulum chaperone protein, 78-kDa glucose-regulated-protein (GRP78), has been observed on the surface of cancer cells, but not on normal tissues. By selectively targeting GRP78 with short-interfering RNA (siRNA), potent GRP78 silencing is anticipated by the RNA interference (RNAi) pathway ...


Sepp1 And Foxm1 Regulate Oxidative Stress-Mediated Radiation Response, Jaimee Claire Eckers Dec 2013

Sepp1 And Foxm1 Regulate Oxidative Stress-Mediated Radiation Response, Jaimee Claire Eckers

Theses and Dissertations

Radiation is a common mode of cancer therapy that is well known to generate reactive oxygen species leading to cell damage and death. However, there are many limitations to radiation therapy including normal tissue toxicity and the presence of quiescent cancer cells that are radio-resistant. There are many factors that regulate normal and cancer cell radiation response including the cellular redox environment which includes a complex network of antioxidants. In this study, two specific objectives will be explored: (A) SEPP1 regulation of normal cell toxicity; and (B) FoxM1 regulation of quiescence-associated radiation resistance in human oral squamous carcinoma cells. Results ...


Effects Of Phytochemicals From Rhodiola Crenulata On Highly Invasive Breast Cancer Cell Lines And Embryonic Models Of Migration, Adaris Rodriguez-Cortes Sep 2013

Effects Of Phytochemicals From Rhodiola Crenulata On Highly Invasive Breast Cancer Cell Lines And Embryonic Models Of Migration, Adaris Rodriguez-Cortes

Open Access Dissertations

The root of the Tibetan plant Rhodiola crenulata is part of eastern traditional medicine. Studies have suggested that members of the Rhodiola genus display anticancer properties. In this study we examine the effect of R. crenulata in a cellular model of invasive breast cancer, this disease being the second cause of cancer death among women in the US. Deregulation of the Wnt/β-catenin pathway has been frequently observed in breast cancers and appears to have a key role in the transformation of benign cells to a malignant form. Although mutations of the Wnt growth factor are rarely observed in cancer ...


Targeted Delivery Of Ribonucleotide Reductase Sirna In Cancer Cells Via Gold Nanoplexes, John Caleb Grenn May 2013

Targeted Delivery Of Ribonucleotide Reductase Sirna In Cancer Cells Via Gold Nanoplexes, John Caleb Grenn

Honors Theses

Cancer treatment has much room for improvement, as therapies today cannot differentiate well between what cells are part of a tumor and which are healthy. Our research involves targeting cancer cells by their overexpressed folic acid receptors, and delivering small interfering RNAs (siRNAs) to silence genes crucial to cell survival by the RNA interference gene knockdown pathway. By using Gaussia luciferase siRNA (siGLuc) as a model for cell delivery, we have been able to test our ability to deliver siRNA via a gold nanoparticle delivery system, also developed in our lab. We also synthesized ribonucleotide reductase siRNA (siRRM2), which will ...


Inflammatory Breast Cancer: The Immune Perspective, Evan N. Cohen May 2013

Inflammatory Breast Cancer: The Immune Perspective, Evan N. Cohen

UT GSBS Dissertations and Theses (Open Access)

Inflammatory breast cancer (IBC) is the most insidious form of locally advanced disease. Although rare and less than 2% of all breast cancer, IBC is responsible for up to 10% of all breast cancer deaths. Despite the name, very little is known about the role of inflammation or immune mediators in IBC. Therefore, we analyzed blood samples from IBC patients and non-IBC patients, as well as healthy donor controls to establish an IBC-specific profile of peripheral blood leukocyte phenotype and function of T cells and dendritic cells and serum inflammatory cytokines.

Emerging evidence suggests that host factors in the microenviromement ...


The Characterization Of Aunp-Pei Conjugates For Sirna Delivery To Cancer Cells”, Albert J. Nosser May 2013

The Characterization Of Aunp-Pei Conjugates For Sirna Delivery To Cancer Cells”, Albert J. Nosser

Honors Theses

Cancer is one of the leading causes of death for people in the United States. Despite the numerous cancer treatments available, many of these chemotherapy treatments cause negative side effects such as hair and weight loss. With this in mind, in the past 15 years, researchers have discovered a mechanism known as RNA interference, which can be used to control certain genes and their activity. This mechanism is based on the function of siRNA molecules, which can be inserted into cells.(12) These siRNA molecules can be manipulated to target and eliminate specific cancer cells. However, these siRNA molecules are ...


The Micronutrient Profile Of The Typical American Diet Enhances Colorectal Carcinogenesis, Stephany Del Carmen Perez Monsanto May 2013

The Micronutrient Profile Of The Typical American Diet Enhances Colorectal Carcinogenesis, Stephany Del Carmen Perez Monsanto

All Graduate Theses and Dissertations

The typical Western dietary pattern is characterized by the consumption of energy-dense, nutrient-poor foods and has been linked to increased risk of colorectal cancer (CRC). Our research group previously developed the total Western diet (TWD) that emulates typical human dietary intakes of macro- (carbohydrates, proteins, and fats) and micronutrients (vitamins and minerals) on an energy density basis for rodents. In the present study, we sought to determine the impact of TWD on biomarkers of metabolic syndrome and obesity in comparison to a commercial 45% fat diet used for models of diet-induced obesity (DIO diet) and the standard basal AIN93G diet ...


Transcriptional Regulation By The Oncogenic Znf217/Corest Complex, Gobi Thillainadesan Apr 2013

Transcriptional Regulation By The Oncogenic Znf217/Corest Complex, Gobi Thillainadesan

Electronic Thesis and Dissertation Repository

The ZNF217 transcription factor is an oncogene found within the 20q13 amplicon and is amplified and overexpressed in many cancers including breast and ovarian. Overexpression of ZNF217 leads to increased cell proliferation, survival, and causes resistance to TGFβ's anti-proliferative effects.

ZNF217 is a core constituent of a transcriptional complex that includes CoREST, HDAC1/2, LSD1, and the CtBP1/2. In this study, I have combined genome-wide biochemical approaches to identify genes directly regulated by ZNF217. I have identified the tumor suppressor and cell cycle inhibitor, p15ink4b, as a direct target of the ZNF217 complex and demonstrated that ZNF217 ...


Characterizing The Contribution Of The Lxcxe Binding Cleft To Prb-Mediated Genome Stability And Tumor Suppression, Courtney H. Coschi Apr 2013

Characterizing The Contribution Of The Lxcxe Binding Cleft To Prb-Mediated Genome Stability And Tumor Suppression, Courtney H. Coschi

Electronic Thesis and Dissertation Repository

Condensation and segregation of mitotic chromosomes are critical processes for cellular propagation and if compromised, can lead to genomic instability. Genomic instability is known to be an active contributor to tumorigenesis, rather than being a by-product of malignant progression. The retinoblastoma protein (pRB) is the prototypic tumor suppressor. Its tumor suppressive properties are linked to its ability to negatively regulate proliferation by inhibiting E2F target gene transcription. Using a gene targeted mouse model defective for interactions mediated by the pRB LXCXE binding cleft that is distinct from E2F binding (Rb1ΔL/ΔL), I have demonstrated that LXCXE-interactions are an essential ...


Interpretation, Stratification And Validation Of Sequence Variants Affecting Mrna Splicing In Complete Human Genome Sequences, Ben C. Shirley Apr 2013

Interpretation, Stratification And Validation Of Sequence Variants Affecting Mrna Splicing In Complete Human Genome Sequences, Ben C. Shirley

Electronic Thesis and Dissertation Repository

The Shannon Human Splicing Pipeline software has been developed to analyze variants on a genome-scale. Evidence is provided that this software predicts variants affecting mRNA splicing. Variants are examined through information-based analysis and the context of novel mutations as well as common and rare SNPs with splicing effects are displayed. Potential natural and cryptic mRNA splicing variants are identified, and inactivating mutations are distinguished from leaky mutations. Mutations and rare SNPs were predicted in genomes of three cancer cell lines (U2OS, U251 and A431), supported by expression analyses. After filtering, tractable numbers of potentially deleterious variants are predicted by the ...


Defining The Mechanism Of Enhanced Cellular Invasion Induced By Mechanical Stimulation, Snehal Sunil Ozarkar Jan 2013

Defining The Mechanism Of Enhanced Cellular Invasion Induced By Mechanical Stimulation, Snehal Sunil Ozarkar

Wayne State University Theses

Metastasis is a multistep process driven by various biochemical and mechanical factors, which eventually leads to formation of secondary tumors. The tumor mass is surrounded by basement membrane (BM) and stroma made of various extracellular matrix (ECM) proteins. During metastasis tumor cells disseminate from the primary tumor, breach the BM, invade the stroma, travel through blood and lymph and colonize tissues distant from the primary tumor. Formation of secondary tumors by metastasis is a leading cause of death in cancer patients. Even though plenty of research has been focused on biochemical factors affecting metastasis, information on role of mechanical factors ...


Effect Of Folate Deficiency And Aging On Mtor Signaling Network In The Liver Of Dna Polymerase B Haploinsufficient Mice, Amanda Lynn Arrabi Jan 2013

Effect Of Folate Deficiency And Aging On Mtor Signaling Network In The Liver Of Dna Polymerase B Haploinsufficient Mice, Amanda Lynn Arrabi

Wayne State University Theses

EFFECT OF FOLATE DEFICIENCY AND AGING ON mTOR SIGNALING NETWORK IN THE LIVER OF DNA POLYMERASE B HAPLOINSUFFICIENT MICE

by

AMANDA ARRABI

August 2013

Advisor: Dr. Ahmad R. Heydari

Major: Nutrition and Food Science

Degree: Masters of Science

The interaction between the dietary nutrients and the human genome causes some alterations in the molecular pathways that could significantly impact the development of cancer. The main approach to such concerns is to closely observe how the diet modifies the gene expressions that control several cellular processes in the human body. Folate deficiency (FD) has established an important role in modulating the ...


Control Of The Tumor Suppressor P53 By Regulating Mdm2 Activity And Stability, Ruchira S. Ranaweera Jan 2013

Control Of The Tumor Suppressor P53 By Regulating Mdm2 Activity And Stability, Ruchira S. Ranaweera

Publicly Accessible Penn Dissertations

p53 is a tumor suppressor that is widely mutated or deleted in cancer cells. Mdm2, an E3 ubiquitin ligase, is the master regulator of p53. It targets p53 for proteasomal degradation, restraining the potent activity of p53 and enabling cell survival and proliferation. There are complex regulatory mechanisms balancing the activity and stability of Mdm2 in a cell. Mdm2 has an extremely short half-life in the unstressed cell and its regulation is not well understood. Like most E3 ligases, Mdm2 can autoubiquitinate. Previously, the sole function of autoubiquitination was thought to be to signal Mdm2 degradation. Here I show that ...


Epigenetic Basis For The Oncogenic Potential Of Idh Mutations, Chao Lu Jan 2013

Epigenetic Basis For The Oncogenic Potential Of Idh Mutations, Chao Lu

Publicly Accessible Penn Dissertations

Although many complex diseases including cancer manifest aberrant cellular metabolism and chromatin structure, the molecular connection between two processes remains poorly understood. The metabolite, α-ketoglurate (αKG), is a critical co-factor for a number of chromatin modifying enzymes. Its structural analogue, 2-hydroxyglutarate (2HG), was recently identified as the product of cancer-associated mutations in isocitrate dehydrogenases (IDH). To determine whether metabolic perturbation can disrupt chromatin remodeling and transcription, I investigated the epigenetic consequences of 2HG-producing IDH mutations. In this thesis, 2HG was demonstrated to be a competitive inhibitor for αKG-dependent chromatin modifiers including TET family DNA hydroxylases and jumonji-C histone demethylases. Expression ...


The Multifunctional Protein Daxx: Studies Of Its Biology And Regulation, And Discovery Of A Novel Function, Trisha Agrawal Jan 2013

The Multifunctional Protein Daxx: Studies Of Its Biology And Regulation, And Discovery Of A Novel Function, Trisha Agrawal

Publicly Accessible Penn Dissertations

Daxx, a multifunctional protein with a diverse set of proposed functions, is ubiquitously expressed and highly conserved through evolution. A primarily nuclear protein, Daxx is able to regulate apoptosis, transcription, and cellular proliferation. Despite many studies into the function of Daxx, its precise role in the cell remains enigmatic. Herein, evidence is presented to expand upon the known anti-apoptotic function of Daxx, to establish Daxx as a novel molecular chaperone, and to further its repertoire of transcriptional targets. As an apoptotic inhibitor, Daxx is known to regulate p53 by stabilizing its main negative regulator, Mdm2, via formation of a ternary ...


Using Spheroids And A Bioluminescent Mouse Model To Determine The Effects Of Ajulemic Acid On Ewing's Scarcoma, Drake Hardy Jan 2013

Using Spheroids And A Bioluminescent Mouse Model To Determine The Effects Of Ajulemic Acid On Ewing's Scarcoma, Drake Hardy

Honors Theses

Ewing's Sarcoma is a pediatric bone cancer with a five-year survival rate of only 30%. New treatment options for this highly aggressive disease are desperately needed. Ajulemic acid (AJA), a synthetic cannabinoid, has been the focus of our research, and has demonstratedd the ability to decrease tumor cell viability and inhibit endothelial cell migration and angiogenesis. Based on these results, AJA is a potential therapeutic agent for Ewing's Sarcoma and other solid pediatric cancers. In order to create a realistic environment in vitro in which to study these tumors, we created 3-dimensional spheroids with three cell types, each ...


The Effect Of Thymidylate Synthase Inhibitors On Bone Marrow Derived Cells In The Intestinal Tumor Microenvironment, Grishma Acharya Jan 2013

The Effect Of Thymidylate Synthase Inhibitors On Bone Marrow Derived Cells In The Intestinal Tumor Microenvironment, Grishma Acharya

Theses and Dissertations

Tumors have come to be known as independently functioning complex organs consisting of cancer cells coexisting with a heterogeneous mixture of host-derived non-neoplastic cells that form the tumor stroma. Tumor survival, progression, and metastasis depend on multiple close interactions between the cancer cells and the tumor stromal cells. These tumor stromal cells are mainly bone marrow derived cells (BMDCs) that are recruited to the primary tumor and sites of metastasis by a variety of signals secreted by the cancer cells. Because of the close interaction between the tumor and the tumor stroma, we propose that tumor stromal cells play an ...


Computational Approaches For Structure Based Drug Design And Protein Structure-Function Prediction, Sai Lakshmana Kumar Vankayala Jan 2013

Computational Approaches For Structure Based Drug Design And Protein Structure-Function Prediction, Sai Lakshmana Kumar Vankayala

Graduate Theses and Dissertations

This dissertation thesis consists of a series of chapters that are interwoven by solving interesting biological problems, employing various computational methodologies. These techniques provide meaningful physical insights to promote the scientific fields of interest. Focus of chapter 1 concerns, the importance of computational tools like docking studies in advancing structure based drug design processes. This chapter also addresses the prime concerns like scoring functions, sampling algorithms and flexible docking studies that hamper the docking successes. Information about the different kinds of flexible dockings in terms of accuracy, time limitations and success studies are presented. Later the importance of Induced fit ...