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Cancer rates vary between people, between cultures, and between tissue types, driven by clinically relevant distinctions in the risk factors that lead to different cancer types. Despite the importance of cancer location in human health, little is known about tissue-specific cancers in non-human animals. We can gain significant insight into

Cancer rates vary between people, between cultures, and between tissue types, driven by clinically relevant distinctions in the risk factors that lead to different cancer types. Despite the importance of cancer location in human health, little is known about tissue-specific cancers in non-human animals. We can gain significant insight into how evolutionary history has shaped mechanisms of cancer suppression by examining how life history traits impact cancer susceptibility across species. Here, we perform multi-level analysis to test how species-level life history strategies are associated with differences in neoplasia prevalence, and apply this to mammary neoplasia within mammals. We propose that the same patterns of cancer prevalence that have been reported across species will be maintained at the tissue-specific level. We used a combination of factor analysis and phylogenetic regression on 13 life history traits across 90 mammalian species to determine the correlation between a life history trait and how it relates to mammary neoplasia prevalence. The factor analysis presented ways to calculate quantifiable underlying factors that contribute to covariance of entangled life history variables. A greater risk of mammary neoplasia was found to be correlated most significantly with shorter gestation length. With this analysis, a framework is provided for how different life history modalities can influence cancer vulnerability. Additionally, statistical methods developed for this project present a framework for future comparative oncology studies and have the potential for many diverse applications.

ContributorsFox, Morgan Shane (Author) / Maley, Carlo C. (Thesis director) / Boddy, Amy (Committee member) / Compton, Zachary (Committee member) / School of Mathematical and Statistical Sciences (Contributor) / School of Molecular Sciences (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Physical activity as a health or nutrition related intervention might stimulate appetite and increase hunger due to increased energy expenditure. This study analyzed the effect of a postprandial 15-minute walk on the hunger and energy intake of 10 obese, pre-diabetic adults. Subjects participated in three 4-hour trials: a walk treatment

Physical activity as a health or nutrition related intervention might stimulate appetite and increase hunger due to increased energy expenditure. This study analyzed the effect of a postprandial 15-minute walk on the hunger and energy intake of 10 obese, pre-diabetic adults. Subjects participated in three 4-hour trials: a walk treatment (consume highly glycemic meal, walk for 15 minutes at a moderate pace, and rest for 4 hours), a fiber treatment (consume highly glycemic meal enriched with soluble fiber and rest for 4 hours), and a control treatment (consume highly glycemic meal without fiber and rest for 4 hours). The effects of each treatment on hunger and energy intake were measured using a Likert scale analysis (ranging from "completely satisfied" to "extremely hungry") at 4 hours post-treatment and pre/ post 24-hour dietary logs. The results showed no significant increase or decrease on hunger or energy intake for both the walk and the fiber treatment compared to the control treatment. This denies the idea that physical activity might increase short-term hunger, and supports the use of physical activity as a viable nutrition related intervention tool.
ContributorsTerrell, Alayna Franci (Author) / Johnston, Carol (Thesis director) / Vega Lopez, Sonia (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor)
Created2015-05
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Despite the 40-year war on cancer, very limited progress has been made in developing a cure for the disease. This failure has prompted the reevaluation of the causes and development of cancer. One resulting model, coined the atavistic model of cancer, posits that cancer is a default phenotype of the

Despite the 40-year war on cancer, very limited progress has been made in developing a cure for the disease. This failure has prompted the reevaluation of the causes and development of cancer. One resulting model, coined the atavistic model of cancer, posits that cancer is a default phenotype of the cells of multicellular organisms which arises when the cell is subjected to an unusual amount of stress. Since this default phenotype is similar across cell types and even organisms, it seems it must be an evolutionarily ancestral phenotype. We take a phylostratigraphical approach, but systematically add species divergence time data to estimate gene ages numerically and use these ages to investigate the ages of genes involved in cancer. We find that ancient disease-recessive cancer genes are significantly enriched for DNA repair and SOS activity, which seems to imply that a core component of cancer development is not the regulation of growth, but the regulation of mutation. Verification of this finding could drastically improve cancer treatment and prevention.
ContributorsOrr, Adam James (Author) / Davies, Paul (Thesis director) / Bussey, Kimberly (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Department of Chemistry and Biochemistry (Contributor) / School of Life Sciences (Contributor)
Created2015-05
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Description
A coincidence reporter construct, consisting of the p21-promoter and two luciferase genes (Firefly and Renilla), was constructed for the screening of drugs that might inhibit Olig2's tumorigenic role in glioblastoma. The reporter construct was tested using an Olig2 inhibitor, HSP990, as well as short hairpin RNA targeting Olig2. Further confirmatory

A coincidence reporter construct, consisting of the p21-promoter and two luciferase genes (Firefly and Renilla), was constructed for the screening of drugs that might inhibit Olig2's tumorigenic role in glioblastoma. The reporter construct was tested using an Olig2 inhibitor, HSP990, as well as short hairpin RNA targeting Olig2. Further confirmatory analysis is needed before the reporter cell line is ready for high-throughput screening at the NIH and lead compound selection.
ContributorsCusimano, Joseph Michael (Author) / LaBaer, Joshua (Thesis director) / Mangone, Marco (Committee member) / Mehta, Shwetal (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor)
Created2014-05
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Description
With obesity and metabolic diseases reaching epidemic levels, it is important to find ways to increase physical activity and improve diet. Previous studies have shown that improvements in mood can increase desire to perform physical activity, and that vitamin C intake is linked to improvements in mood. Based on this,

With obesity and metabolic diseases reaching epidemic levels, it is important to find ways to increase physical activity and improve diet. Previous studies have shown that improvements in mood can increase desire to perform physical activity, and that vitamin C intake is linked to improvements in mood. Based on this, two hypotheses were formed and tested to investigate the effect on physical activity levels and mood states from vitamin C supplementation at a dose of one gram per day in the form of a novel functional food. Thirty-one college students or faculty at Arizona State University were screened from a pool of applicants and placed into either a vitamin C or placebo group; all participants received the novel functional food to eat daily for four weeks. Serum levels of vitamin C, weight, height, BMI, body fat percentage, mood, and physical activity were measured before and after the functional food intervention. Vitamin C changed significantly through the course of the study in the experimental group. Baseline data for participants showed a positive correlation between vitamin C status and vigor, and a negative correlation between vitamin C status and weight and BMI. Physical activity was not related to vitamin C status, according to baseline data, and it did not significantly change over the course of the study. The results indicate that variance in BMI can be attributed to vitamin C status, but the study should be refined and tested again.
ContributorsHelland, Stephanie Lynn (Author) / Johnston, Carol (Thesis director) / Sweazea, Karen (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / Department of Psychology (Contributor) / School of Life Sciences (Contributor) / Graduate College (Contributor)
Created2014-05
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Description
Exercise is a great boon to both the health of individuals and the national as a whole. Exercise provides a wide range of significant and well established benefits to both physical and psychological health, with many benefits that are still being discovered. The effects of exercise on health are somewhat

Exercise is a great boon to both the health of individuals and the national as a whole. Exercise provides a wide range of significant and well established benefits to both physical and psychological health, with many benefits that are still being discovered. The effects of exercise on health are somewhat unique, as exercise is one of a limited number of ways to improve health that is not harm a reduction strategy, but instead increases health through direct benefit, rather than increasing health by decreasing damage and harm. Support is also given to the proposal that individuals are in best position to determine the intensity of exercise and to choose primary activities to participate in, in order to provide near maximum physical and psychological benefit, with the understanding that frequency of exercise is of the upmost importance for benefit. The accessibility of exercise and the tremendous health benefit of exercise, makes exercise a huge asset in reducing the exorbitant health care spending and improving mediocre health outcomes in this country; a reasonable goal as numerous countries have better health the United States, even though the United States spends the more than any other country on health.
ContributorsRael, Ashur Scott (Author) / Kashiwagi, Dean (Thesis director) / Kashiwagi, Jacob (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / School of Film, Dance and Theatre (Contributor)
Created2015-05
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Description
The purpose of this project is to explore the benefit of using prodrugs in chemotherapy, as well as to explain the concept of angiogenesis and the importance of this process to tumor development. Angiogenesis is the formation of new blood capillaries that are necessary for the survival of a

The purpose of this project is to explore the benefit of using prodrugs in chemotherapy, as well as to explain the concept of angiogenesis and the importance of this process to tumor development. Angiogenesis is the formation of new blood capillaries that are necessary for the survival of a tumor, as a tumor cannot grow larger than 1-2 mm3 without developing its own blood supply. Vascular disrupting agents, such as iodocombstatin, a derivative of combretastatin, can be used to effectively cut off the blood supply to a growing neoplasm, effectively inhibiting the supply of oxygen and nutrients needed for cell division Thus, VDAs have a very important implication in terms of the future of chemotherapy. A prodrug, defined as an agent that is inactive in the body until metabolized to yield the drug itself, was synthesized by combining iodocombstatin with a β-glucuronide linker. The prodrug is theoretically hydrolyzed in the body to afford the active drug by β-glucuronidase, an enzyme that is produced five times as much by cancer cells as by normal cells. This effectively creates a “magic-bullet” form of chemotherapy, known as Direct Enzyme Prodrug Therapy (DEPT).
ContributorsClark, Caroline Marie (Author) / Pettit, George Robert (Thesis director) / Melody, Noeleen (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor)
Created2015-05
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Description
This project aims to address the current protocol regarding the diagnosis and treatment of traumatic brain injury (TBI) in medical industries around the world. Although there are various methods used to qualitatively determine if TBI has occurred to a patient, this study attempts to aid in the creation of a

This project aims to address the current protocol regarding the diagnosis and treatment of traumatic brain injury (TBI) in medical industries around the world. Although there are various methods used to qualitatively determine if TBI has occurred to a patient, this study attempts to aid in the creation of a system for quantitative measurement of TBI and its relative magnitude. Through a method of artificial evolution/selection called phage display, an antibody that binds highly specifically to a post-TBI upregulated brain chondroitin sulfate proteoglycan called neurocan has been identified. As TG1 Escheria Coli bacteria were infected with KM13 helper phage and M13 filamentous phage in conjunction, monovalent display of antibody fragments (ScFv) was performed. The ScFv bind directly to the neurocan and from screening, phage that produced ScFv's with higher affinity and specificity to neurocan were separated and purified. Future research aims to improve the ScFv characteristics through increased screening toward neurocan. The identification of a highly specific antibody could lead to improved targeting of neurocan post-TBI in-vivo, aiding researchers in quantitatively defining TBI by visualizing its magnitude.
ContributorsSeelig, Timothy Scott (Author) / Stabenfeldt, Sarah (Thesis director) / Ankeny, Casey (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2015-05
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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

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
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Description
Cancer rates in our nearest relatives are largely unknown. Comparison of human cancer rates with other primates should help us to understand the nature of our susceptibilities to cancer. Data from deceased primates was gathered from 3 institutions, the Duke Lemur Center, San Diego Zoo, and Jungle Friends primate sanctuary.

Cancer rates in our nearest relatives are largely unknown. Comparison of human cancer rates with other primates should help us to understand the nature of our susceptibilities to cancer. Data from deceased primates was gathered from 3 institutions, the Duke Lemur Center, San Diego Zoo, and Jungle Friends primate sanctuary. This data contained over 400 unique individuals across 45 species with information on cancer incidence and mortality. Cancer incidence ranged from 0-71% and cancer mortality ranged from 0-67%. We used weighted phylogenetic regressions to test for an association between life history variables (specifically body mass and lifespan) and cancer incidence as well as mortality. Cancer incidence did not correlate with both body mass and lifespan (p>.05) however, cancer mortality did (p<.05). However, it is uncertain if the variables can be used as reliable predictors of cancer, because the data come from different organizations. This analysis presents cancer incidence rates and cancer mortality rates in species where it was previously unknown, and in some primate species, is surprisingly high. Microcebus murinus(grey mouse lemur) appear to be particularly vulnerable to cancer, mostly lymphomas. Further studies will be required to determine the causes of these vulnerabilities.
ContributorsWalker, William Charles (Author) / Maley, Carlo (Thesis director) / Boddy, Amy (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05