Matching Items (80)
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- All Subjects: Cancer
- All Subjects: Obesity
- Creators: School of Life Sciences
- Member of: Barrett, The Honors College Thesis/Creative Project Collection
Description
Cancer remains one of the leading killers throughout the world. Death and disability due to lung cancer in particular accounts for one of the largest global economic burdens a disease presents. The burden on third-world countries is especially large due to the unusually large financial stress that comes from late tumor detection and expensive treatment options. Early detection using inexpensive techniques may relieve much of the burden throughout the world, not just in more developed countries. I examined the immune responses of lung cancer patients using immunosignatures – patterns of reactivity between host serum antibodies and random peptides. Immunosignatures reveal disease-specific patterns that are very reproducible. Immunosignaturing is a chip-based method that has the ability to display the antibody diversity from individual sera sample with low cost. Immunosignaturing is a medical diagnostic test that has many applications in current medical research and in diagnosis. From a previous clinical study, patients diagnosed for lung cancer were tested for their immunosignature vs. healthy non-cancer volunteers. The pattern of reactivity against the random peptides (the ‘immunosignature’) revealed common signals in cancer patients, absent from healthy controls. My study involved the search for common amino acid motifs in the cancer-specific peptides. My search through the hundreds of ‘hits’ revealed certain motifs that were repeated more times than expected by random chance. The amino acids that were the most conserved in each set include tryptophan, aspartic acid, glutamic acid, proline, alanine, serine, and lysine. The most overall conserved amino acid observed between each set was D - aspartic acid. The motifs were short (no more than 5-6 amino acids in a row), but the total number of motifs I identified was large enough to assure significance. I utilized Excel to organize the large peptide sequence libraries, then CLUSTALW to cluster similar-sequence peptides, then GLAM2 to find common themes in groups of peptides. In so doing, I found sequences that were also present in translated cancer expression libraries (RNA) that matched my motifs, suggesting that immunosignatures can find cancer-specific antigens that can be both diagnostic and potentially therapeutic.
ContributorsShiehzadegan, Shima (Author) / Johnston, Stephen (Thesis director) / Stafford, Phillip (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2015-12
Description
Background: High risk types of human papillomavirus (HPV) are known to cause cancer, including cervical (99%) and oropharyngeal cancer (70%). HPV type 16 is the most common subtype. Three antigens that are critical for integration or tumor progression are E2, E6 and E7. In this study, we developed a systematic approach to identify naturally-processed HPV16-derived HLA class I epitopes for immunotherapy development. Methods: K562 cells, which lack HLA expression, were transduced with each HPV16 antigen using lentivirus and supertransfected with HLA-A2 by nucleofection. Stable cell lines expressing each antigen were selected for and maintained throughout the investigation. In order to establish a Gateway-compatible vector for robust transient gene expression, a Gateway recombination expression cloning cassette was inserted into the commercial Lonza pMAX GFP backbone, which has been experimentally shown to display high transfection expression efficiency. GFP was cloned into the vector and plain K562 cells were transfected with the plasmid by nucleofection. Results: Expression of K562-A2 was tested at various time points by flow cytometry and A2 expression was confirmed. Protein expression was shown for the transduced K562 E7 by Western blot analysis. High transfection efficiency of the pMAX_GFP_Dest vector (up to 97% GFP+ cells) was obtained 48 hours post transfection, comparable to the commercial GFP-plasmid. Conclusion: We have established a rapid system for target viral antigen co-expression with single HLA molecules for analysis of antigen presentation. Using HPV as a model system, our goal is to identify specific antigenic peptide sequences to develop immunotherapeutic treatments for HPV-associated cancers.
ContributorsVarda, Bianca Marie (Author) / Anderson, Karen (Thesis director) / Borges, Chad (Committee member) / Krishna, Sri (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Current studies in Multiple Myeloma suggest that patient tumors and cell lines cluster separately based on gene expression profiles. Hyperdiploid patients are also extremely underrepresented in established human myeloma cell lines (HMCLs). This suggests that the average HMCL model system does not accurately represent the average myeloma patient. To investigate this question we performed a combined CNA and SNV evolutionary comparison between four myeloma tumors and their established HMCLs (JMW-1, VP-6, KAS-6/1-KAS-6/2 and KP-6). We identified copy number changes shared between the tumors and their cell lines (mean of 74 events - 59%), those unique to patients (mean of 21.25 events - 17%), and those only in the cell lines (mean of 30.75 events \u2014 24%). A relapse sample from the JMW-1 patient showed 58% similarity to the primary diagnostic tumor. These data suggest that, on the level of copy number abnormalities, HMCLs show equal levels of evolutionary divergence as that observed within patients. By exome sequencing, patient tumors were 71% similar to their representative HMCLs, with ~12.5% and ~16.5% of SNVs unique to the tumors and HMCLs respectively. The HMCLs studied appear highly representative of the patient from which they were derived, with most differences associated with an enrichment of sub-populations present in the primary tumor. Additionally, our analysis of the KP-6 aCGH data showed that the patient's hyperdiploid karyotype was maintained in its respective HMCL. This discovery confirms the establishment and validation of a novel and potentially clinically relevant hyperdiploid HMCL that could provide a major advance in our ability to understand the pathogenesis and progression of this prominent patient population.
ContributorsBenard, Brooks Avery (Author) / Keats, Jonathan (Thesis director) / Anderson, Karen (Committee member) / Jelinek, Diane (Committee member) / School of Molecular Sciences (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
This project studies trends in the corporate wellness sphere and what companies are currently doing to promote wellness among their employees. It outlines several key studies on diabetes and obesity and shows the economic impact these lifestyle diseases have on the healthcare system. It also covers how the Affordable Care Act is supporting preventative behavior, how companies are promoting wellness, and the long-term benefits of doing so. It examines the effectiveness of current corporate wellness programs, highlights best practices, and identifies areas for improvement. These findings are used to propose a realistic, holistic corporate wellness plan that will promote wellness among employees and reduce a companies' long-term healthcare costs.
ContributorsRobottom, Danielle P. (Author) / Hall, Rick (Thesis director) / Levinson, Simin (Committee member) / Barrett, The Honors College (Contributor) / Department of Marketing (Contributor) / W. P. Carey School of Business (Contributor)
Created2014-05
Description
This project explores a variety of ways of framing the problem of obesity, beginning with a multidisciplinary assessment of genetic, environmental, cultural, nutritional, and socioeconomic factors involved in the structure and the consequences of each frame. How obesity is framed as a problem has a profound impact on the kinds of solutions that may be deemed scientifically appropriate. But frames are not entirely evidence-based, inasmuch as political and moral values infuse debates about the nature of obesity. Drawing on interdisciplinary resources from bioethics and the philosophy of science, I strive to offer strategic insight in to how to navigate the complexity of these issues.
ContributorsYanamandra, Meghana (Author) / Robert, Jason (Thesis director) / Wharton, Christopher (Committee member) / Drago, Mary (Committee member) / Barrett, The Honors College (Contributor) / School of Sustainability (Contributor) / School of Life Sciences (Contributor) / School of Human Evolution and Social Change (Contributor)
Created2014-05
Description
This project studies trends in the corporate wellness sphere and what companies are currently doing to promote wellness among their employees. It outlines several key studies on diabetes and obesity and shows the economic impact these lifestyle diseases have on the healthcare system. It also covers how the Affordable Care Act is supporting preventative behavior, how companies are promoting wellness, and the long-term benefits of doing so. It examines the effectiveness of current corporate wellness programs, highlights best practices, and identifies areas for improvement. These findings are used to propose a realistic, holistic corporate wellness plan that will promote wellness among employees and reduce a companies' long-term healthcare costs.
ContributorsRobottom, Danielle P. (Author) / Hall, Rick (Thesis director) / Levinson, Simin (Committee member) / Barrett, The Honors College (Contributor) / Department of Marketing (Contributor) / W. P. Carey School of Business (Contributor)
Created2014-05
Description
The long-term survival of patients with glioblastoma multiforme is compromised by the tumor's proclivity for local invasion into the surrounding normal brain. These invasive cells escape surgery and display resistance to chemotherapeutic- and radiation-induced apoptosis. We have previously shown that tumor necrosis factor-like weak inducer of apoptosis (TWEAK), a member of the tumor necrosis factor superfamily, can stimulate glioma cell invasion and survival via binding to the fibroblast growth factor-inducible 14 (Fn14) receptor and subsequent activation of the Rac1/NF-kappaB pathway. In addition, we have reported previously that Fn14 is expressed at high levels in migrating glioma cells in vitro and invading glioma cells in vivo. Here we demonstrate that TWEAK can act as a chemotactic factor for glioma cells, a potential process to drive cell invasion into the surrounding brain tissue. Specifically, we detected a chemotactic migration of glioma cells to the concentration gradient of TWEAK. Since Src family kinases (SFK) have been implicated in chemotaxis, we next determined whether TWEAK:Fn14 engagement activated these cytoplasmic tyrosine kinases. Our data shows that TWEAK stimulation of glioma cells results in a rapid phosphorylation of the SFK member Lyn as determined by multiplex Luminex assay and verified by immunoprecipitation. Immunodepletion of Lyn by siRNA oligonucleotides suppressed the chemoattractive effect of TWEAK on glioma cells. We hypothesize that TWEAK secretion by cells present in the glioma microenvironment induce invasion of glioma cells into the brain parenchyma. Understanding the function and signaling of the TWEAK-Fn14 ligand-receptor system may lead to development of novel therapies to therapeutically target invasive glioma cells.
ContributorsJameson, Nathan Meade (Author) / Anderson, Karen (Thesis director) / Lake, Douglas (Committee member) / Tran, Nhan (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2013-05
Description
Obesity is now an epidemic in the United States and scientists must work to approach it from a unique angle. The focus of my thesis is the application of brown adipose tissue as a combatant for fat loss in the body. Unused as adults, brown adipose tissue increases metabolism and mitochondrial function to burn more fat in individuals that cannot lose weight conventionally. Current research works to introduce safe hormonal pathways in the sympathetic nervous system to generate more of this tissue.
ContributorsGrade, Neenah Young (Author) / Morse, Lisa (Thesis director) / Appel, Christy (Committee member) / Mayol-Kreiser, Sandra (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2013-05
Description
Thirty six percent of Americans are obese and thirty three percent are overweight; obesity has become a known killer in the U.S. yet its prevalence has maintained a firm grasp on the U.S. population and continues to spread across the globe as other countries slowly adopt the American lifestyle. A survey was compiled collecting demographic and body mass index (BMI) information, as well as Tanofsky-Kraff’s (2009) “Assess Eating in the Absence of Hunger” survey questions. The survey used for this study was emailed out to Arizona State University students in Barrett, The Honors College, and the ASU School of Nutrition and Health Promotion listservs. A total of 457 participants completed the survey, 72 males and 385 females (mean age, 24.5±7.7 y; average body mass index (BMI), 23.4 ± 4.8 [a BMI of 25-29.9 is classified as overweight]). When comparing BMI with the living situation, 71% of obese students were living at home with family versus off campus with friends or alone. For comparison, 45% of normal weight students lived at home with family. These data could help structure prevention plans targeting college students by focusing on weight gain prevention at the family level. Results from the Tanofsky-Kraff (2009) survey revealed there was not a significant relationship between external or physical cues and BMI in men or women, but there was a significant positive correlation between emotional cues and BMI in women only. Anger and sadness were the emotional cues in women related to initiating consumption past satiation and consumption following several hours of fasting. Although BMI was inversely related to physical activity in this sample (r = -0.132; p=0.005), controlling for physical activity did not impact the significant associations of BMI with anger or sadness (P>0.05). This information is important in targeting prevention programs to address behavioral change and cognitive awareness of the effects of emotion on over-consumption.
ContributorsGarza, Andrea Marie (Author) / Johnston, Carol (Thesis director) / Jacobs, Mark (Committee member) / Coletta, Dawn (Committee member) / Barrett, The Honors College (Contributor) / Department of Psychology (Contributor) / School of Life Sciences (Contributor)
Created2013-05
Description
Cancer is one of the leading causes of death in the world and represents a tremendous burden on patients, families and societies. S. Typhimurium strains are specifically attracted to compounds produced by cancer cells and could overcome the traditional therapeutic barrier. However, a major problem with using live attenuated Salmonella as anti-cancer agents is their toxicity at the dose required for therapeutic efficacy, but reducing the dose results in diminished efficacy. In this project, we explored novel means to reduce the toxicity of the recombinant attenuated Salmonella by genetically engineering those virulence factors to facilitate maximal colonization of tumor tissues and reduced fitness in normal tissues. We have constructed two sets of Salmonella strains. In the first set, each targeted gene was knocked out by deletion of the gene. In the second set, the predicted promoter region of each gene was replaced with a rhamnose-regulated promoter, which will cease the synthesis of these genes in vivo, a rhamnose-free environment.
ContributorsBenson, Lee Samuel (Author) / Kong, Wei (Thesis director) / Martin, Thomas (Committee member) / Lake, Douglas (Committee member) / Barrett, The Honors College (Contributor) / Department of Psychology (Contributor) / Center for Infectious Diseases and Vaccinology (Contributor) / School of Life Sciences (Contributor)
Created2013-05