Matching Items (27)
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- All Subjects: Cancer
- Creators: Department of Psychology
Description
Cancer is the second leading cause of death in the United States and novel methods of treating advanced malignancies are of high importance. Of these deaths, prostate cancer and breast cancer are the second most fatal carcinomas in men and women respectively, while pancreatic cancer is the fourth most fatal in both men and women. Developing new drugs for the treatment of cancer is both a slow and expensive process. It is estimated that it takes an average of 15 years and an expense of $800 million to bring a single new drug to the market. However, it is also estimated that nearly 40% of that cost could be avoided by finding alternative uses for drugs that have already been approved by the Food and Drug Administration (FDA). The research presented in this document describes the testing, identification, and mechanistic evaluation of novel methods for treating many human carcinomas using drugs previously approved by the FDA. A tissue culture plate-based screening of FDA approved drugs will identify compounds that can be used in combination with the protein TRAIL to induce apoptosis selectively in cancer cells. Identified leads will next be optimized using high-throughput microfluidic devices to determine the most effective treatment conditions. Finally, a rigorous mechanistic analysis will be conducted to understand how the FDA-approved drug mitoxantrone, sensitizes cancer cells to TRAIL-mediated apoptosis.
ContributorsTaylor, David (Author) / Rege, Kaushal (Thesis advisor) / Jayaraman, Arul (Committee member) / Nielsen, David (Committee member) / Kodibagkar, Vikram (Committee member) / Dai, Lenore (Committee member) / Arizona State University (Publisher)
Created2013
Description
Alzheimer's disease (AD) is the most common type of dementia, affecting one in nine people age 65 and older. One of the most important neuropathological characteristics of Alzheimer's disease is the aggregation and deposition of the protein beta-amyloid. Beta-amyloid is produced by proteolytic processing of the Amyloid Precursor Protein (APP). Production of beta-amyloid from APP is increased when cells are subject to stress since both APP and beta-secretase are upregulated by stress. An increased beta-amyloid level promotes aggregation of beta-amyloid into toxic species which cause an increase in reactive oxygen species (ROS) and a decrease in cell viability. Therefore reducing beta-amyloid generation is a promising method to control cell damage following stress. The goal of this thesis was to test the effect of inhibiting beta-amyloid production inside stressed AD cell model. Hydrogen peroxide was used as stressing agent. Two treatments were used to inhibit beta-amyloid production, including iBSec1, an scFv designed to block beta-secretase site of APP, and DIA10D, a bispecific tandem scFv engineered to cleave alpha-secretase site of APP and block beta-secretase site of APP. iBSec1 treatment was added extracellularly while DIA10D was stably expressed inside cell using PSECTAG vector. Increase in reactive oxygen species and decrease in cell viability were observed after addition of hydrogen peroxide to AD cell model. The increase in stress induced toxicity caused by addition of hydrogen peroxide was dramatically decreased by simultaneously treating the cells with iBSec1 or DIA10D to block the increase in beta-amyloid levels resulting from the upregulation of APP and beta-secretase.
ContributorsSuryadi, Vicky (Author) / Sierks, Michael (Thesis advisor) / Nielsen, David (Committee member) / Dai, Lenore (Committee member) / Arizona State University (Publisher)
Created2014
Description
This purpose of this thesis study was to examine variables of the "War on Cancer" frame, loss-gain prime, and patient gender on treatment decision for advanced cancer patients. A total of 291 participants (141 females) participated in an online survey experiment and were randomly assigned to one of eight possible conditions, each of which were comprised of a combination of one of two levels for three total independent variables: war frame ("War on Cancer" frame or neutral frame), loss-gain prime (loss prime or gain prime), and patient gender (female or male). Each of the three variables were operationalized to determine whether or not the exposure to the war on cancer paradigm, loss-frame language, or male patient gender would increase the likelihood of a participant choosing a more aggressive cancer treatment. Participants read a patient scenario and were asked to respond to questions related to motivating factors. Participants were then asked to report preference for one of two treatment decisions. Participants were then asked to provide brief demographic information in addition to responding to questions about military history, war attitudes, and cancer history. The aforementioned manipulations sought to determine whether exposure to various factors would make a substantive difference in final treatment decision. Contrary to the predicted results, participants in the war frame condition (M = 3.85, SD = 1.48) were more likely to choose the pursuit of palliative care (as opposed to aggressive treatment) than participants in the neutral frame condition (M = 3.54, SD = 1.23). Ultimately, these significant findings suggest that there is practical information to be gained from treatment presentation manipulations. By arming healthcare providers with a more pointed understanding of the nuances of treatment presentation, we can hope to empower patients, their loved ones, and healthcare providers entrenched in the world of cancer treatment.
ContributorsKnowles, Madelyn Ann (Author) / Kwan, Virginia S. Y. (Thesis director) / Presson, Clark (Committee member) / Salamone, Damien (Committee member) / Department of Psychology (Contributor) / School of Human Evolution and Social Change (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Background: Noninvasive MRI methods that can accurately detect subtle brain changes are highly desirable when studying disease-modifying interventions. Texture analysis is a novel imaging technique which utilizes the extraction of a large number of image features with high specificity and predictive power. In this investigation, we use texture analysis to assess and classify age-related changes in the right and left hippocampal regions, the areas known to show some of the earliest change in Alzheimer's disease (AD). Apolipoprotein E (APOE)'s e4 allele confers an increased risk for AD, so studying differences in APOE e4 carriers may help to ascertain subtle brain changes before there has been an obvious change in behavior. We examined texture analysis measures that predict age-related changes, which reflect atrophy in a group of cognitively normal individuals. We hypothesized that the APOE e4 carriers would exhibit significant age-related differences in texture features compared to non-carriers, so that the predictive texture features hold promise for early assessment of AD. Methods: 120 normal adults between the ages of 32 and 90 were recruited for this neuroimaging study from a larger parent study at Mayo Clinic Arizona studying longitudinal cognitive functioning (Caselli et al., 2009). As part of the parent study, the participants were genotyped for APOE genetic polymorphisms and received comprehensive cognitive testing every two years, on average. Neuroimaging was done at Barrow Neurological Institute and a 3D T1-weighted magnetic resonance image was obtained during scanning that allowed for subsequent texture analysis processing. Voxel-based features of the appearance, structure, and arrangement of these regions of interest were extracted utilizing the Mayo Clinic Python Texture Analysis Pipeline (pyTAP). Algorithms applied in feature extraction included Grey-Level Co-Occurrence Matrix (GLCM), Gabor Filter Banks (GFB), Local Binary Patterns (LBP), Discrete Orthogonal Stockwell Transform (DOST), and Laplacian-of-Gaussian Histograms (LoGH). Principal component (PC) analysis was used to reduce the dimensionality of the algorithmically selected features to 13 PCs. A stepwise forward regression model was used to determine the effect of APOE status (APOE e4 carriers vs. noncarriers), and the texture feature principal components on age (as a continuous variable). After identification of 5 significant predictors of age in the model, the individual feature coefficients of those principal components were examined to determine which features contributed most significantly to the prediction of an aging brain. Results: 70 texture features were extracted for the two regions of interest in each participant's scan. The texture features were coded as 70 initial components andwere rotated to generate 13 principal components (PC) that contributed 75% of the variance in the dataset by scree plot analysis. The forward stepwise regression model used in this exploratory study significantly predicted age, accounting for approximately 40% of the variance in the data. The regression model revealed 5 significant regressors (2 right PC's, APOE status, and 2 left PC by APOE interactions). Finally, the specific texture features that contributed to each significant PCs were identified. Conclusion: Analysis of image texture features resulted in a statistical model that was able to detect subtle changes in brain integrity associated with age in a group of participants who are cognitively normal, but have an increased risk of developing AD based on the presence of the APOE e4 phenotype. This is an important finding, given that detecting subtle changes in regions vulnerable to the effects of AD in patients could allow certain texture features to serve as noninvasive, sensitive biomarkers predictive of AD. Even with only a small number of patients, the ability for us to determine sensitive imaging biomarkers could facilitate great improvement in speed of detection and effectiveness of AD interventions..
ContributorsSilva, Annelise Michelle (Author) / Baxter, Leslie (Thesis director) / McBeath, Michael (Committee member) / Presson, Clark (Committee member) / School of Life Sciences (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
The purpose of this thesis study was to examine whether the "war on cancer" metaphor influences cancer perception and treatment decision. A total of 249 undergraduates (152 females) from a large southwestern university participated in an online survey experiment and were either randomly assigned to the control condition (N=123) or to the war prime condition (N=126). Participants in the control condition did not receive the metaphor manipulation while participants in the war prime condition received the subtle "war on cancer" metaphor prime. After the prime was given, participants read a scenario, answered questions related to the situation, and responded to demographic questions. The results suggested that, compared to participants in the no-prime condition, participants exposed to the war metaphor were more likely to (a) view melanoma as an acute disease, (b) choose chemotherapy over molecular tests, and (c) prefer more aggressive treatment. These findings illustrated the unintended consequences of the "war on cancer" slogan. The results were encouraging and in the predicted direction, but the effect size was small. The discussion section described possible future directions for research.
ContributorsShangraw, Ann Mariah (Author) / Kwan, Virginia (Thesis director) / Neuberg, Steven (Committee member) / Cavanaugh Toft, Carolyn (Committee member) / Barrett, The Honors College (Contributor) / Department of Psychology (Contributor)
Created2015-05
Does assisted cycle therapy influence activities of daily living in older adults with Down syndrome?
Description
The aim of this study is to examine the relationship between Assisted Cycle Therapy, leisure time activity levels, fine motor control, and grip force in older adults with Down syndrome (DS), all of which affect activities of daily living (ADL) and therefore quality of life. This is relevant because this particular group is at risk for developing early onset Alzheimer's disease (AD), which presents itself uniquely in this population. The parent or guardian of six participants with DS completed Godin's Leisure Time Exercise Questionnaire and the participants themselves completed Purdue Pegboard and grip force assessments before and after an 8-week exercise intervention. The results were inconsistent with past research, with no change being seen in fine motor control or grip force and a decrease being seen in leisure activity. These findings are indicative of the importance of the effect of fatigue on leisure activity as well as maintaining elevated heart rate throughout exercise interventions.
ContributorsGomez, Elizabeth Danielle (Author) / Ringenbach, Shannon (Thesis director) / Coon, David (Committee member) / Barrett, The Honors College (Contributor) / T. Denny Sanford School of Social and Family Dynamics (Contributor) / Department of Psychology (Contributor)
Created2015-05
Description
In our modern world the source of for many chemicals is to acquire and refine oil. This process is becoming an expensive to the environment and to human health. Alternative processes for acquiring the final product have been developed but still need work. One product that is valuable is butanol. The normal process for butanol production is very intensive but there is a method to produce butanol from bacteria. This process is better because it is more environmentally safe than using oil. One problem however is that when the bacteria produce too much butanol it reaches the toxicity limit and stops the production of butanol. In order to keep butanol from reaching the toxicity limit an adsorbent is used to remove the butanol without harming the bacteria. The adsorbent is a mesoporous carbon powder that allows the butanol to be adsorbed on it. This thesis explores different designs for a magnetic separation process to extract the carbon powder from the culture.
ContributorsChabra, Rohin (Author) / Nielsen, David (Thesis director) / Torres, Cesar (Committee member) / Barrett, The Honors College (Contributor) / Chemical Engineering Program (Contributor)
Created2015-05
Description
Cancer is a disease that occurs in many and perhaps all multicellular organisms. Current research is looking at how different life history characteristics among species could influence cancer rates. Because somatic maintenance is an important component of a species' life history, we hypothesize the same ecological forces shaping the life history of a species should also determine its cancer susceptibility. By looking at varying life histories, potential evolutionary trends could be used to explain differing cancer rates. Life history theory could be an important framework for understanding cancer vulnerabilities with different trade-offs between life history traits and cancer defenses. Birds have diverse life history strategies that could explain differences in cancer suppression. Peto's paradox is the observation that cancer rates do not typically increase with body size and longevity despite an increased number of cell divisions over the animal's lifetime that ought to be carcinogenic. Here we show how Peto’s paradox is negatively correlated for cancer within the clade, Aves. That is, larger, long-lived birds get more cancer than smaller, short-lived birds (p=0.0001; r2= 0.024). Sexual dimorphism in both plumage color and size differ among Aves species. We hypothesized that this could lead to a difference in cancer rates due to the amount of time and energy sexual dimorphism takes away from somatic maintenance. We tested for an association between a variety of life history traits and cancer, including reproductive potential, growth rate, incubation, mating systems, and sexual dimorphism in both color and size. We found male birds get less cancer than female birds (9.8% vs. 11.1%, p=0.0058).
ContributorsDolan, Jordyn Nicole (Author) / Maley, Carlo (Thesis director) / Harris, Valerie (Committee member) / Boddy, Amy (Committee member) / School of Molecular Sciences (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
Alzheimer's disease (AD), which currently affects approximately 5.4 million Americans, is a type of dementia, which causes memory, cognitive, and behavioral problems. AD is among the top 10 leading causes of death in the United States, typically affecting people ages 65 and older. Beta-Amyloid (Aβ) is an Alzheimer's target protein, which starts as a single protein, but can misfold and bind to itself, forming larger chains and eventually fibrils and plaques of Aβ in the brain. Antibodies that bind to different regions and sizes of Aβ may prevent progression into a more toxic stage. The antibody worked with in this thesis, A4 scFv, binds to oligomeric Aβ. The objective of this antibody research is to optimize the production of functional antibodies, specifically A4, through modifications in the scFv growth process, in order to enhance the discovery of possible diagnostics and therapeutics for Alzheimer's disease. In order to produce functional A4 antibody, four complex sugars were tested in the E. Coli bacterial culture growth media that expresses the desired antibody. The sugars: sucrose, glucose, mannitol, and sorbitol were used in the growth process to improve the yield of functional antibody. Through the steps of growth, purification, and dialysis, the sugar sorbitol was found to provide the optimal results of ending functional antibody concentration. Once an ample amount of functional A4 scFv is produced, it can be used in assays as a biomarker for Alzheimer's disease.
ContributorsDolberg, Taylor Brianne (Author) / Sierks, Michael (Thesis director) / Nielsen, David (Committee member) / Barrett, The Honors College (Contributor) / Chemical Engineering Program (Contributor) / School of Sustainability (Contributor)
Created2014-05
Description
The nuclear pore complex is a structure that is found in the nuclear envelope. The nuclear pore complex is made of proteins known as nucleoporins, or Nups. There are many classes of Nups, one of which is Nups with phenylalanine-guanine repeats (FG-Nups). The FG-Nups help control the transport of material through the nuclear pore complex. One type of FG-Nup is NupL2. Previous mRNA data have shown that there is lower expression of NupL2 in Alzheimer's Disease brains than there is in control brains. However, these data are specific to mRNA expression, and do not necessarily extend to NupL2 protein levels. This study focuses on NupL2 levels in non-diseased samples and Alzheimer's Disease samples. Immunohistochemistry (IHC) with 3,3'-diaminobenzidine was performed on temporal neo-cortical brain tissue. Western blots were also performed to quantify the protein levels in non-diseased samples and Alzheimer's Disease samples, and were completed using middle temporal gyrus lysates. The IHC results show that there is more NupL2 protein expression in non-diseased samples than there is in Alzheimer's Disease samples. Likewise, the western blot data show higher NupL2 protein levels in non-diseased samples than in Alzheimer's Disease samples. Both the IHC data and the western blot data indicate that there are higher NupL2 expression levels in non-diseased samples than in Alzheimer's Disease samples. Decreased NupL2 expression in Alzheimer's Disease may indicate that it is not functioning properly. This could lead to the leaking of material between the nucleoplasm and the cytoplasm, which may in turn contribute to Alzheimer's Disease pathogenesis.
ContributorsKulkarni, Neha Uday (Author) / Coleman, Paul (Thesis director) / Mastroeni, Diego (Committee member) / School of Life Sciences (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05