Life Sciences Commons^™

Structural Investigation Of Atp-Utilizing Enzymes: Structures Involved In H+ Homeostasis And The Proliferation Of Hormone-Dependent Cancers, Zacariah Louis Hildenbrand

Open Access Theses & Dissertations

ATP is a multifunctional nucleotide considered to be the "molecular unit of currency" of intracellular energy transfer. ATP is utilized ubiquitously for the transport of chemical energy within the cell in addition to acting as a substrate in the regulation of many metabolic and signaling transduction pathways such as kinase-mediated signaling cascades. Interestingly, the functional mechanisms of many enzymes require the binding of ATP to trigger key structural and conformational changes that ultimately result in enzyme-directed catalysis. Two of the most omnipresent ATPases within the cell include the V-ATPase rotary proton pump and the Hsp90 protein-folding chaperone. Structural and biochemical …

Adjacent Slice Prostate Cancer Prediction To Inform Maldi Imaging Biomarker Analysis, Shao-Hui Chuang, Xiaoyan Sun, Lisa Cazares, Julius Nyalwidhe, Dean Troyer, O. John Semmes, Jiang Li, Frederic D. Mckenzie, Nico Karssemeijer (Ed.), Ronald M. Summers (Ed.)

Electrical & Computer Engineering Faculty Publications

Prostate cancer is the second most common type of cancer among men in US [1]. Traditionally, prostate cancer diagnosis is made by the analysis of prostate-specific antigen (PSA) levels and histopathological images of biopsy samples under microscopes. Proteomic biomarkers can improve upon these methods. MALDI molecular spectra imaging is used to visualize protein/peptide concentrations across biopsy samples to search for biomarker candidates. Unfortunately, traditional processing methods require histopathological examination on one slice of a biopsy sample while the adjacent slice is subjected to the tissue destroying desorption and ionization processes of MALDI. The highest confidence tumor regions gained from the …

Expression And Function Of Hypoxia Inducible Factor-1 Alpha In Human Melanoma Under Non-Hypoxic Conditions, Caroline N. Mills, Sandeep S. Joshi, Richard M. Niles

Biochemistry and Microbiology

Background

Hypoxia inducible factor-1 alpha (HIF-1α) protein is rapidly degraded under normoxic conditions. When oxygen tensions fall HIF-1α protein stabilizes and transactivates genes involved in adaptation to hypoxic conditions. We have examined the normoxic expression of HIF-1α RNA and protein in normal human melanocytes and a series of human melanoma cell lines isolated from radial growth phase (RGP), vertical growth phase (VGP) and metastatic (MET) melanomas.

Results

HIF-1α mRNA and protein was increased in RGP vs melanocytes, VGP vs RGP and MET vs VGP melanoma cell lines. We also detected expression of a HIF-1α mRNA splice variant that lacks part …

An Examination Of Chimpanzee Use In Human Cancer Research, Jarrod Bailey

Laboratory Experiments Collection

Advocates of chimpanzee research claim the genetic similarity of humans and chimpanzees make them an indispensable research tool to combat human diseases. Given that cancer is a leading cause of human death worldwide, one might expect that if chimpanzees were needed for, or were productive in, cancer research, then they would have been widely used. This comprehensive literature analysis reveals that chimpanzees have scarcely been used in any form of cancer research, and that chimpanzee tumours are extremely rare and biologically different from human cancers. Often, chimpanzee citations described peripheral use of chimpanzee cells and genetic material in predominantly human …

Anticancer Properties Of Research-Grade Hydrastis Canadensis (Goldenseal) And Characterization Of Its Effect On The Mdr1-Encoded Phosphoglycoprotein Efflux Pump, Sara Garrett

All Theses

Multiple drug resistance (MDR) in tumors, observed both in vivo and in vitro, is generally attributed to efflux-mediated reduced drug accumulation via mdr1/P-gp. Notoriously chemoresistant colorectal cancers exhibit the highest P-gp expression, account for 9% of all cancer deaths, and are the third most common cancer in men and women. P-gp, a 170kDa protein, contains twelve transmembrane segments with two ATP-binding domains used to extrude intracellular compounds of broad specificity against a concentration gradient. Studies concerning natural health products are becoming more prevalent in the search for safe anti-P-gp remedies and Hydrastis canadensis (goldenseal) was studied for its anti-cancer properties. …

Mechanisms Of Induced Cell Death In Bluetongue Virus Challenged Human Cell Lines, Justin Darrel Hoopes

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Bluetongue virus (BTV) is a pathogenic member of the Reoviridae family. BTV does not cause disease in humans, but is capable of selectively infecting and killing certain transformed human cell lines. Understanding BTV's oncotrophism may lead to new therapeutics for treating cancer. This study focused on the underlying mechanisms of BTV-induced cell death in carcinoma cell lines. It was our hypothesis that BTV infects human carcinoma transformed cells, produces mRNA and protein, induces a strong inflammatory response, induces mitogen activated protein kinase (MAPK)-based pro-apoptotic signaling, inhibits PKB-based signaling, and eventually kills the cell by inducing apoptosis.

Three carcinoma cell lines …

Inducing A Normal Phenotype In Breast Epithelial Cells Using A Three-Dimensional Basement Membrane Extract Culture System: A Study On The Reversion Of Cancer, Ross H. Booth

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Experimentally, traditional developmental models and transgenic animals consistently underscore the importance of studying cell behavior in the correct tissue context. However, live animal experimentation is inherently complex, and systematic assessment of the effects of individual variables, such as cell shape and matrix compliance on cell behavior, is extremely difficult at best. Two-dimensional monolayer culture of key individual cell types has provided abundant, fundamental information on cell response, but cannot be used to show the normal phenotype of breast epithelial cells. Furthermore, their results often fail to translate into in vivo and clinical studies. It has been previously established that normal …

Preparation, Separation, Purification, Characterization And Human Cell Line Anti-Cancer Evaluation Of Rice Bran Peptides, Arvind Kannan

Graduate Theses and Dissertations

Bioactive compounds are revolutionizing the nutritional and medicinal world with their inherent disease-fighting properties. A wide range of functional groups fall under the category of imparting health benefits. Compounds from both animal and plant origins have been generated as bioactive agents that have opened up new vistas for alternative medicine and natural healing. For example, in a debilitating disease like cancer, these compounds can act to suppress or delay the underlying pathology over and above the conventional treatment strategies involving drugs or chemotherapy. In other words conventional and invasive therapy, although still considered appropriate at certain stages of cancer, their …

Role Of The P21 Protein In The Fanconi Anemia Pathway, Mae Shen

Senior Honors Projects

Our bodies are constantly exposed to a variety of substances that damage our DNA, such as ultraviolet radiation, environmental chemicals, and the reactive by-products of our metabolism. To prevent the harmful effects that may result from such damage, our cells possess multiple DNA repair mechanisms. However, if their ability to repair damaged DNA is somehow impaired, cells are more likely to accumulate potentially harmful mutations, including those that may lead to the development of cancer.

In Fanconi anemia (FA), a rare recessive genetic disorder, a defect in a DNA repair pathway results in increased sensitivity to a particular type of …

Rational Drug Design: An Information Driven Approach To The Design Of An Anthracycline Analog, Charlene Rebecca Young

Boise State University Theses and Dissertations

Over the past fifty years anthracyclines have been used to treat a wide variety of cancers. Combination therapies with anthracyclines have the potential to greatly increase treatment success. Despite the great potential of anthracyclines in the treatment of cancer, their use has been limited due to the risk of chronic cardiotoxicity. The reduction of anthracyclines to an alcohol metabolite has been linked to the development of cardiotoxic side effects. One of the principal enzymes responsible for catalyzing the formation of the anthracycline alcohol metabolite is human carbonyl reductase 1(HCBR). Controlling the reduction of anthracyclines by HCBR may offer a means …

Light-Regulated Sampling Of Protein Kinase Activity (Ii), Collaborative Project

Dyson College- Seidenberg School of CSIS : Collaborative Projects and Presentations

This entry adheres to the use of the quad chart template to provide a succinct description only of the current research project undertaken by the participants. It provides for the following information

1. Participants and Affiliations
2. Overall Project Goals
3. Illustrative picture
4. Specific research/artistic/pedagogic foci

Myf5 Does Not Induce Apoptosis In Skeletal Myoblasts But Is Regulated By Oncogenic Ras Expression, Alexander Phillip Talarico

ETD Archive

Skeletal myogenesis is initiated by a family of muscle regulatory factors (MRFs) composed of the transcription factors MyoD, Myf5, MRF4, and myogenin. Of these, MyoD was the first discovered, is the most studied, and plays a well-characterized role in skeletal myoblast determination and differentiation. Our laboratory has also discovered that MyoD plays an important role in the apoptotic process that occurs in a subpopulation of myoblasts induced to differentiate. Expression of oncogenic Ras is known to inhibit myoblast differentiation and to decrease the expression of MyoD mRNA and protein. Our laboratory was the first to report that expression of oncogenic …

Live-Cell Studies On Mitotic Slippage In Humans, Daniela A. Brito

Legacy Theses & Dissertations (2009 - 2024)

Checkpoints are regulatory pathways that control the order and timing of specific cell-cycle events. In the presence of unattached/weakly-attached kinetochores, the mitotic checkpoint (MC) arrests cells in mitosis by inhibiting the degradation of cyclin B, the regulatory subunit of Cdk1 (cyclin dependent kinase 1). Checkpoints do not arrest cells permanently, and escaping mitosis with an unsatisfied MC requires cyclin B/Cdk1 inactivation. In yeast, this occurs through an “adaptation” mechanism involving inhibitory phosphorylations and/or Cdk1-inhibitors. To determine how vertebrate cells escape mitosis when the MC cannot be satisfied I conducted live-cell imaging and immunofluorescence studies on nocodazole-treated rat kangaroo (PtK) and …

Comparative Cytotoxicity Of An Fda-Approved Cancer Drug To Extracts Of Atriplex Confertifolia On Human Breast And Cervical Cancer Cells, Christopher James Capua

Theses and Dissertations

The severity and number of people affected by cancer is a worldwide problem with millions of people affected annually. The search for treatment and cures of cancer continues to be a global effort. As part of this global effort, many natural products have been tested against cancer cell lines, most from plants located in tropical regions. However, this study reports that extracts of Atriplex confertifolia, a native North American plant, has significant bioactivity against human breast cancer cell lines MCF-7, 435, and 231, and HeLa cells (cervical cancer cells). The bioactivity of A. confertifolia extracts of these cells lines was …

Treg Depletion Inhibits Efficacy Of Cancer Immunotherapy: Implications For Clinical Trials., James Curtin, Marianela Candolfi, Tamer Fakhouri, Chunyan Liu, Anderson Alden, Matthew Edwards, Pedro Lowenstein, Maria Castro

Articles

BACKGROUND: Regulatory T lymphocytes (Treg) infiltrate human glioblastoma (GBM); are involved in tumor progression and correlate with tumor grade. Transient elimination of Tregs using CD25 depleting antibodies (PC61) has been found to mediate GBM regression in preclinical models of brain tumors. Clinical trials that combine Treg depletion with tumor vaccination are underway to determine whether transient Treg depletion can enhance anti-tumor immune responses and improve long term survival in cancer patients. FINDINGS: Using a syngeneic intracrabial glioblastoma (GBM) mouse model we show that systemic depletion of Tregs 15 days after tumor implantation using PC61 resulted in a decrease in Tregs …

Sensitization To Trail-Induced Apoptosis In K-Ras 12 Mutant Pancreatic Cancer Cells By Bitc, Christina Ann Wicker

Browse all Theses and Dissertations

Pancreatic adenocarcinoma is an aggressive cancer with a greater than 95% mortality rate and short survival after diagnosis. Chemotherapeutic resistance hinders successful treatment. This resistance is associated with mutations within codon 12 of the K-Ras gene (K-Ras 12), which is present in over 90% of all pancreatic adenocarcinomas. Codon 12 mutations maintain Ras in a constitutively active state leading to continuous cellular proliferation. Our study determined if TRAIL resistance in pancreatic adenocarcinomas with K-Ras 12 mutations could be overcome by first sensitizing the cells with Benzyl isothiocyanate (BITC). BITC is a component of cruciferous vegetable extracts and a cell cycle …

Mdm2 Amplification In Nih3t3l1 Preadipocytes Leads To Mdm2 Elevation In Terminal Adipogenesis, Vaughn Litteral

Browse all Theses and Dissertations

The p53 protein is a tumor suppressor protein that is mutated or non-functional in nearly all cancers. The Mdm2 protein has the ability to functionally inactivate p53 and these two proteins have been studied extensively in the context of cellular proliferation. In this study, expression of the murine double minute 2 (mdm2) gene was examined in the mouse NIH3T3L1 cell line. Under the proper conditions, the immortalized NIH3T3L1 cells have the ability to differentiate from fibroblasts to adipocytes (Green et al., 1975). This well characterized cell line provides an excellent model to study mdm2 in differentiation. While evaluating the regulation …

Role Of Vegf-C In Proliferation And Migration In A Cancer Model, Emily Marie Benke

Theses and Dissertations

Head and neck cancer ranks high among the most common cancers world wide. In addition, there is a high recurrence rate, as well as a high prevalence of loco-regional tumor spread. Among many factors contributing to metastasis is vascular endothelial cell growth factor C. VEGF-C is primarily an inducer of new lymph vessel formation, typically during embryogenesis; however, some advanced cancers show a significant increase in VEGF-C expression, suggesting a role in metastasis. In the current study, the effects of VEGF-C expression were tested in HN12 cells, which are highly metastatic and known to express high levels of the chemokine …

Pyridinium Bis-Retinoids A2-Dopamine And A2-Cadaverine: Implications In Age-Related Macular Degeneration And Cancer, Mckenzie Ruth Pew

Theses and Dissertations

Age-related macular degeneration (AMD) is the leading cause of blindness in the United States of America. The pyridinium bis-retinoid A2-ethanolamine (A2E) has been implicated to play a role in AMD. We have observed novel pyridinium bis-retinoids through melanolipofuscin and human RPE extractions that may also play a role in the pathology of AMD. We have begun the construction of an amino-retinoid library in order to identify these ocular compounds. The compounds from the amino-retinoid library are also used in a targeted and triggered drug delivery system for treating cancer. Folic acid is coupled with the amino-retinoids to specifically target cancer …

Evaluating Satisfaction And Benefit From Nutrition Counseling From A Registered Dietitian Among Head And Neck Cancer Patients Receiving Radiation Therapy., Lori E. Watson

Electronic Theses and Dissertations

The purpose of this study was to determine if patients with head or neck cancer receiving radiation were satisfied with the nutrition counseling they were receiving and if they obtained any benefit. Radiation to the head or neck region promotes side effects such as taste changes and chewing and swallowing difficultly that decrease food and fluid intake. A reduction in nutrients leads to weight loss, and weight loss in cancer patients increases the risk of morbidity and morality as well as decreases quality of life. Subjects were recruited from a local cancer treatment facility and a survey was administered. Subjects …

Colon Cancer-- A Silent Killer, Katelyn Carman

Whittier Scholars Program

Colon cancer is the second leading cause of cancer deaths annually. The goal of this research is to (a) increase awareness of colon cancer by identifying anatomical and physiological changes that occur when cancerous polyps are present, (b) describe different genetic mutations that occur, (c) discuss preventative screening procedures and (d) explain different treatment options for colon cancer patients. There will be an additional section on the genetic link to colon cancer because it is thought to be the main cause of some cancerous polyps. Being aware of the potential risks associated with colon cancer can save lives.

The Role Of Sphingosine Kinase 2 In Cell Growth And Apoptosis, Heidi M. Sankala

Theses and Dissertations

Two isoforms of sphingosine kinase (SphK) catalyze the formation of sphingosine-1-phosphate (SIP). Whereas, SphKl stimulates cell growth and survival, it was found that when overexpressed in mouse NIH 3T3 fibroblasts SphK2 enhances caspase-dependent apoptosis in response to serum deprivation, independently of S1P receptors. Sequence analysis revealed that SphK2 contains a 9 amino acid motif similar to that present in BH3-only proteins. Studies showed that the BH3-only domain, catalytic activity, endoplasmic reticulum (ER) stress, and uptake of calcium by the mitochondria may all contribute to the apoptotic effects of overexpressed SphK2 in NIH 3T3 cells. Further studies in human carcinoma cells …

Effects Of Cxcl8 Overexpression On Tumor Cell Proliferation And Migration In An Hnscc Cell Model, Emil Paul Christofakis

Theses and Dissertations

Head and neck squamous cell carcinoma is the 6th most common malignancyworldwide. Recently, a link between cancer and inflammation has been found. Mediatingthis relationship are the chemotactic cytokines known as chemokines. CXCL8 (Interleukin-8), a CXC ELR+ Chemokine mainly responsible for neutrophil chemoattraction, has beenimplicated in increased tumor proliferation, migration and angiogenesis. The current studytests the effects of CXCL8 on the tumor proliferation and metastasis. By genetically modifying cells to knockdown or overexpress the CXCL8 gene we tested its biological rolein head and neck cancer progression. Overexpression of CXCL8 in HN4 tumor cells withlow endogenous CXCL8 levels was found to increase …

Need For Cognition And Message Complexity In Motivating Fruit And Vegetable Intake Among Callers To The Cancer Information Service, Pamela Williams-Piehota, Judith Pizarro, Stephanie A. Navarro Silvera, Linda Mowad, Peter Salovey

Department of Public Health Scholarship and Creative Works

This field experiment examined the impact of an individual's need for cognition (NFC; the tendency to enjoy thinking deeply about issues), complex versus simple messages, and the interaction of NFC and message type on encouraging fruit and vegetable consumption. Callers to the Cancer Information Service of the National Cancer Institute (N = 517) were asked to participate in the experiment at the end of their call. Individual NFC was assessed, and participants were assigned randomly to receive a telephone message promoting fruit and vegetable consumption that was either complex and multifaceted or simple and straightforward. Similarly constructed brochures were mailed …

Role Of Mdm2 In Cell Growth Regulation, Rebecca Anne Frum

Theses and Dissertations

MDM2 has been shown to induce G0-Gl/S phase arrest. To determine the cell cycle step targeted by MDM2, flow cytometry was employed to detect induction of events during the G1-S phase transition in MDM2-arrested cells. MDM2 overexpression does not prevent expression of cyclin D, cyclin D-CDK mediated phosphorylation of Rb or cyclin E in normal, immortal or tumor-derived cells. However, MDM2 down-regulates cyclin A expression specifically in normal cells, which is associated with G1 arrest. The domain of MDM2 capable of this function is located within its N-terminal 58-109 amino acids. To down-regulate cyclin A, MDM2 requires a functional pl6/Brg …

The Epigenomic Viewpoint On Cellular Differentiation Of Myeloid Progenitor Cells As It Pertains To Leukemogenesis, Vincent E. Sollars

Biochemistry and Microbiology

The new millennium has brought with it a surge of research in the field of epigenetics. This has included advances in our understanding of stem cell characteristics and mechanisms of commitment to cell lineages prior to differentiation. The nature of stem cells is similar to that of malignant cells in that they have unlimited self-renewal and protection from apoptosis, leading researchers to suspect that stem cells are the target of oncogenesis. This review will explore the idea of how epigenetic control of gene expression may contribute to mechanisms controlling differentiation of myeloid progenitor cells and its importance to our understanding …

The Effect Of Rooibos Tea (Aspalathus Linearis) On The Survival And Transformation Of C3h-Bt1 Mouse Fibroblasts, Krista M. Beach, Paul J. Smith

Honors Capstones

Capstone submitted as a graduation requirement for the BSU Honors Program.

Identification Of The Rna Cis-Elements That Interact With Srp30a To Regulate The Alternative Splicing Of Caspase 9 Pre-Mrna, Prabhat Mukerjee

Theses and Dissertations

Studies have shown that the alternative splicing of caspase 9 and the phospho-status of SR proteins, a conserved family of splicing factors, are regulated by chemotherapy and de novo ceramide via the action of protein phosphatase-1 (PP1). Two RNA splice variants are derived from the caspase 9 gene, pro-apoptotic caspase 9a and anti-apoptotic caspase 9b, via alternative splicing by either the inclusion or exclusion of an exon 3, 4, 5, and 6 cassette. In this study, the link between SR proteins and the alternative splicing of caspase 9 was established. Sequence analysis of the exon 3, 4, 5, and 6 …

In Vitro And In Vivo Anti-Angiogenic Activities Of Milk Sphingolipids, Rishipal Rastrapal Bansode

LSU Doctoral Dissertations

Anti-angiogenic therapies aimed at halting new blood vessel formation are now being extensively studied as inhibitors of excessive angiogenesis. Conversely, compounds with ability to stimulate angiogenesis are being considered as a therapeutic approach for insufficient angiogenesis. Food-borne bioactive compounds such as genistein, resveratrol, curcumin, the Bowman-Birk inhibitor, and catechins are being potentially established as good candidates for angioprevention. The aim of our study was to determine the anti-or pro-angiogenic activity of milk-based glycosphingolipids such as C6-ceramide (Cer), Sphingomyelin (SPM) and Glucosylceramide (GluCer), in vitro, using breast cancer (MCF-7), colon cancer (Caco-2) and prostate cancer (DU-145) cell-lines, on angiogenic factors such …

Tumor Response Tcf-4/Β-Catenin Regulatory Elements For Enhancing Cancer Gene Therapies, Saurabh Kumar Gupta

Theses and Dissertations in Biomedical Sciences

Mutations in the adenomatous polyposis coli gene are frequently associated with progression of colon carcinoma and most other types of epithelial carcinomas. This usually results in stabilization of β-catenin protein levels, followed by transactivation of Tcf-4/β-catenin responsive genes. The effectiveness of a Tcf-4/β-catenin transcriptional enhancer element in combination with a c-fos or carcinoembryonic antigen promoter was tested for its ability to act as a tumor specific regulator of gene expression in a panel of human tumor and normal cell lines. Luciferase reporter assays indicated enhanced activity of the Tcf-4/β-catenin transcriptional element only in tumor cell lines, with minimal activities in …