Life Sciences Commons^™

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. …

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, the …

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

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

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, …

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

Dissertations & 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 …

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 …

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 normally …

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, p15^ink4b, as a direct target of the ZNF217 complex and demonstrated that ZNF217 represses the …

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 (Rb1^ΔL/ΔL), I have demonstrated that LXCXE-interactions are an …

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 …

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 …

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 …

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

USF Tampa 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 …

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 …

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 of which …