Matching Items (127)
Description
The focus of this project was to look at alternative treatments for endocrine resistant breast cancer (ERBC), which are breast cancers that have become resistant to hormone therapies such as Tamoxifen or aromatase inhibitors. The first part of this project involves investigating the relationship between histone de-acetylase inhibitor Vorinostat and Tamoxifen in MCF7 G11 cells, Tamoxifen resistant sub-clones, according to the PSOC Time grant. The second part involves targeting the androgen receptor (AR) in MCF7 sub-clones with AR antagonists, Bicalutamide and MDV3100, and investigating the possible usage of AR as a biomarker, due to over-expression of AR in ERBC, in accordance with the Mayo ASU Seed Grant.
The synergistic effects between Vorinostat and Tamoxifen observed through a phase II study on breast cancer patients resistant to hormone therapy may involve more than the modulation of ER-alpha to reverse Tamoxifen resistance in ERBC cells. RT-qPCR of genes expressed in Tamoxifen resistant cells, trefoil factor 1(TFF1) and v-myc avian myelocytomatosis viral oncogene homolog (MYC), were evaluated along with ESR1 and Diablo as a control. MYC was observed to have increased expression in the treated cells, whereas the other genes had a decrease in their expression levels after the cells were treated for 3 days with Vorinostat IC30 of 1 µM. As for targeting the AR, MCF7 Tamoxifen sensitive and resistant cells were not affected by the AR antagonists to determine an IC50. The cell viability for all MCF7 sub-clones only decreased for high concentrations of 5.56 µM - 50 µM in Bicalutamide and 16.67 µM – 50 µM of MDV1300. Furthermore, hormone depletion of MCF7 G11 Tamoxifen resistant sub-clones did not show a great response to DHT stimulation or the AR antagonists. In the RT-qPCR, the MCF7 G11 cells showed an increase in mRNA expression for ER, AR, and PR after 4 hours of treatment with estradiol. As for the DHT treatment, ER, AR, PR, and PSA had a minimal increase in the fold change, but the fold change in AR was less than in the estradiol treatment. The Mayo Clinic will investigate the possible usage of AR as a biomarker through immunohistochemistry.
The synergistic effects between Vorinostat and Tamoxifen observed through a phase II study on breast cancer patients resistant to hormone therapy may involve more than the modulation of ER-alpha to reverse Tamoxifen resistance in ERBC cells. RT-qPCR of genes expressed in Tamoxifen resistant cells, trefoil factor 1(TFF1) and v-myc avian myelocytomatosis viral oncogene homolog (MYC), were evaluated along with ESR1 and Diablo as a control. MYC was observed to have increased expression in the treated cells, whereas the other genes had a decrease in their expression levels after the cells were treated for 3 days with Vorinostat IC30 of 1 µM. As for targeting the AR, MCF7 Tamoxifen sensitive and resistant cells were not affected by the AR antagonists to determine an IC50. The cell viability for all MCF7 sub-clones only decreased for high concentrations of 5.56 µM - 50 µM in Bicalutamide and 16.67 µM – 50 µM of MDV1300. Furthermore, hormone depletion of MCF7 G11 Tamoxifen resistant sub-clones did not show a great response to DHT stimulation or the AR antagonists. In the RT-qPCR, the MCF7 G11 cells showed an increase in mRNA expression for ER, AR, and PR after 4 hours of treatment with estradiol. As for the DHT treatment, ER, AR, PR, and PSA had a minimal increase in the fold change, but the fold change in AR was less than in the estradiol treatment. The Mayo Clinic will investigate the possible usage of AR as a biomarker through immunohistochemistry.
ContributorsVorachitti, Merica (Author) / LaBaer, Joshua (Thesis director) / Anderson, Karen (Committee member) / Gonzalez, Laura (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Department of Chemistry and Biochemistry (Contributor)
Created2014-05
Description
The United States is experiencing an increase in the prevalence and influence of complementary and alternative medicine (CAM) in patient healthcare, reflecting the increasingly positive public and professional attitudes on the use of CAM therapies. Despite the growing presence of CAM in U.S. healthcare, there are still many barriers to integration. This study aims to reveal the attitudes of conventional, integrative and CAM practitioners concerning the major challenges of CAM's integration, explore their proposed solutions, and reveal any discrepancies in these attitudes among different types of practitioners. Twenty-eight practitioners were interviewed on the challenges in the five facets of CAM's integration: integration into hospitals, integration into medical schools, insurance coverage for CAM, licensing & regulation of CAM practitioners, and clinical research in CAM. The overall positive attitudes on the benefits of CAM's integration support previous research on the subject; however, the conventional practitioners were unable to extend these benefits to real-world application, and they were unaware of many of the challenges facing CAM's integration. The CAM practitioners attributed many of the problems facing integration to the inability of CAM's philosophy to comply with the current ideology of medical academia, health insurance model, and laws that govern the licensing and regulation of medical practitioners. The CAM and integrative practitioners perceived there to be a large resistance from conventional practitioners, specifically concerning the integration of CAM into education, providing insurance coverage for CAM, and the licensing and regulation of CAM practitioners. They attributed this to a perceived lack of research on safe and effective treatments in CAM. The conventional practitioner responses reflected this weariness of treatment effectiveness in their responses. However, the CAM and integrative practitioners believed these claims to be largely inaccurate, and constructed by the influence and manipulation of large-scale medical corporations and organizations. The participants believed that more evidence-based research in CAM, and increased public awareness in CAM therapies will force conventional practitioners to increase their knowledge in CAM, helping to alleviate their fears and skepticism of CAM therapies. By easing these concerns, dialogue can occur among practitioners of different modalities that will help to ensure a smooth integration of CAM and will raise the quality of patient healthcare by providing safe and effective resources for alternate forms of treatment.
ContributorsJohnston, Shantele Hanna Lee (Author) / Hruschka, Daniel (Thesis director) / Hurlbut, Ben (Committee member) / Barrett, The Honors College (Contributor) / School of International Letters and Cultures (Contributor) / School of Human Evolution and Social Change (Contributor)
Created2014-05
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 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
Description
The pathogenesis of type 1 diabetes (T1D) is still not fully understood in the scientific community. Evidence has shown that viral infections are one of the important environmental factors associated with the disease development. Seven of the top T1D related viruses were selected to study the prevalence of viral humoral response in T1D patients using our innovative protein array platform called Nucleic Acid Programmable Protein Array (NAPPA). In this study, each viral gene was individually captured using various PCR based techniques, cloned into a protein expression vector, and assembled as the first version of T1D viral protein array. Humoral responses of IgG, IgA, and IgM were examined. Although each class of immunoglobulin generated a wide-range of reactivity, responses to various viral proteins from different proteins were observed. In summary, we captured most of the T1D related viral genes, established viral protein expression on the protein array, and displayed the serum response on the viral protein array. The successful progress will help to fulfill the long term goal of testing the viral infection hypothesis in T1D development.
ContributorsDavis, Amy Darlene (Author) / LaBaer, Joshua (Thesis director) / Qiu, Ji (Committee member) / Desi, Paul (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor)
Created2013-05
Description
Fat-stigma has become a popular topic of research in recent years as obesity and Western ideals have made their way around the globe. Previous studies have found that the internalization and expression of body norms can vary dramatically depending on location, gender, and many other cultural factors. Differing levels of body satisfaction have been linked to the internalization of these norms, and the development of low body esteem can result in many physical and emotional problems. Although there is an abundance of research on the topic of fat-stigma, few studies have investigated the related, but seemingly independent, topic of the ideal thin body. Furthermore, limited research has looked directly at body size stereotypes in Guatemala, and those that have, focused solely on Guatemala City. Furthermore, no previous cross-cultural analyses were found comparing body norms among US and rural Guatemalan adolescents. By surveying 9-10 year old students in Acatenango, Guatemala and Phoenix, Arizona, this study compared the preferences as well as stereotypes for average, thin, and fat body sizes in these two contexts. The results of this study illustrate a contrast between a fat-negative and a thin-negative culture, and highlight the complexity of the emergence of body norms around the world. We find that, in contrast to previous studies, neither the western ideal thin body nor obesity stereotypes have been internalized in Acatenango. Furthermore, negative evaluations of fat bodies and positive evaluations of thin bodies seem to be made independently of each other. Americans had a much higher prejudice against fat children and were more likely to be thin-positive (OR=1.997), while Guatemalans were more likely to be thin-negative. On average, the American students were much more polarized in their judgments on different body sizes, and experienced greater levels of body dissatisfaction. Finally, American students favored an ideal figure over one size smaller than Guatemalan students. Results suggest that there are still rural communities that have not been entirely affected by the spread of western body norms.
ContributorsCole, Dawn Michelle (Author) / Maupin, Jonathan (Thesis director) / Hruschka, Daniel (Committee member) / Barrett, The Honors College (Contributor) / School of Geographical Sciences and Urban Planning (Contributor) / School of Human Evolution and Social Change (Contributor)
Created2013-12
Description
Africa is the area of the largest economic water scarcity on earth, with multiple countries, political systems, and geographies involved. Additionally, water scarcity affects more countries in sub-Saharan African than anywhere else on earth, with consequences like waterborne diseases, loss of agricultural development, educational setbacks, and security threats. This thesis synthesizes data on the diverse geographies and politics involved in building a sustainable African water system. It presents historical and present technologies, costs, and problems implementing sustainable potable water solutions, and suggests regional differences and individualized solutions, pointing out advantages and disadvantages of damming, boreholes, open wells, open-source water, and sewer systems. It goes on to discuss grant programs for water and wastewater solutions and technologies. Finally it addresses two divergent, yet equally important data models for African water planning, combining their contributions in order to gain insight into the problem that neither alone can. The research overlaps aquifer and demographic data to see where water should be a priority in Africa. The author finds that hydrology as well as demographic data, when combined, point to the greatest water need in the Sahel. However, many growing cities are situated in areas with high aquifer levels making borehole technology some of the most economical as well as sustainable water sourcing. Recommendations include cultural humility, attention to political and environmental consequences of solutions, and cost-effective ways of addressing the lack of access to clean drinking water in Africa.
ContributorsBarbur, Denisa Teodora (Author) / Gaughan, Monica (Thesis director) / Hruschka, Daniel (Committee member) / Barrett, The Honors College (Contributor) / School of International Letters and Cultures (Contributor) / School of Human Evolution and Social Change (Contributor)
Created2014-05
Description
Protein AMPylation is a recently discovered and relatively unstudied post-translational modification (PTM). AMPylation has previously been shown to play an important role in metabolic regulation and host pathogenesis in bacteria, but the recent identification of potential AMPylators across many species in every domain of life has supported the possibility that AMPylation could be a more fundamental and physiologically significant regulatory PTM. For the first time, we characterized the auto-AMPylation capability of the human protein SOS1 through in vitro AMPylation experiments using full-length protein and whole-domain truncation mutants. We found that SOS1 can become AMPylated at a tyrosine residue possibly within the Cdc25 domain of the protein, the Dbl homology domain is vital for efficient auto-AMPylation activity, and the C-terminal proline-rich domain exhibits a complex regulatory function. The proline-rich domain alone also appears to be capable of catalyzing a separate, unidentified covalent self-modification using a fluorescent ATP analogue. Finally, SOS1 was shown to be capable of catalyzing the AMPylation of two endogenous human protein substrates: a ubiquitous, unidentified protein of ~49kDa and another breast-cancer specific, unidentified protein of ~28kDa.
ContributorsOber-Reynolds, Benjamin John (Author) / LaBaer, Joshua (Thesis director) / Borges, Chad (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / School of Life Sciences (Contributor)
Created2014-05
Description
The purpose of this study was to investigate how the human-animal relationship affects one's willingness to seek veterinary care for a pet. It is important to understand this topic because past research has shown that companion animals play a very large role in the lives of many people. However, there has been a decline in the frequency of veterinary visits despite an increase in the number of pets. The variables of the human-animal relationship that were tested were one's views on the intelligence of a pet and its ability to feel emotions, and the closeness one feels to a pet. Demographic factors were also considered. The dependent variable of one's willingness to seek veterinary care was measured by the amount one would spend on veterinary treatment for a healthy pet, the amount one would spend on an older pet, and the responsibility one feels for the health and well-being of one's pet. The study revealed that the closeness one feels to a pet and one's views on a pet's ability to feel emotion both have a positive correlation with one's willingness to seek veterinary care for a pet. However, there was no correlation between one's views on the intelligence of a pet and one's willingness to seek veterinary care, and there was only a very slight correlation between income and one's willingness to seek veterinary care. Understanding these factors could be important in ensuring that companion animals receive the necessary care to promote their health and well-being.
ContributorsMagnussen, Hailey Eve (Author) / Hruschka, Daniel (Thesis director) / Risley-Curtiss, Christina (Committee member) / Barrett, The Honors College (Contributor) / T. Denny Sanford School of Social and Family Dynamics (Contributor) / School of Life Sciences (Contributor)
Created2014-05
Description
Curanderos are Hispanic traditional healers who attend to their clients through spiritual, natural, and physical techniques. Recent studies have shown that a subset of the Hispanic population refer to these healers for HIV and STD treatment and believe they are important in a collaborative targeted HIV intervention. Thus, curanderos were interviewed and the lay population of Phoenix was sampled in order to get a better idea of the utility of these healers in an HIV prevention effort targeted at the Hispanic community. Due to the limitations of this study there was not sufficient enough data to make significant conclusions; however the interviews with the curanderos were surprising in the they had significant roles as healers in the Phoenix area, patients have referred to them for HIV and STD treatment, and a couple of the healers have integrated western medical knowledge into their practice.
ContributorsMartinez, Justin Anthony (Author) / Maupin, Jonathan (Thesis director) / Hruschka, Daniel (Committee member) / Aguilera, Miguel (Committee member) / Barrett, The Honors College (Contributor) / School of Human Evolution and Social Change (Contributor) / School of Life Sciences (Contributor)
Created2013-05
Description
AMPylation is a post-translation modification that has an important role in the survival of many bacterial pathogens by affecting the host cell's molecular signaling. In the course of studying this intercellular manipulation, there has only been modest progression in the identification of the enzymes with AMPylation capabilities (AMPylators) and their respective targets. The reason for these minimal developments is the inability to analyze a large subset of these proteins. Therefore, to increase the efficiency of the identification and characterization of the proteins, Yu et al developed a high-throughput non-radioactive discovery platform using Human Nucleic Acid Programmable Protein Arrays (NAPPA) and a validation platform using bead-based assays. The large-scale unbiased screening of potential substrates for two bacterial AMPylators containing Fic domain, VopS and IbpAFic2, had been performed and dozens of novel substrates were identified and confirmed. With the efficiency of this method, the platform was extended to the identification of novel substrates for a Legionella virulence factor, SidM, containing a different adenylyl transferase domain. The screening was performed using NAPPA arrays comprising of 10,000 human proteins, the active AMPylator SidM, and its inactive D110/112A mutant as a negative control. Many potential substrates of SidM were found, including Rab GTPases and non-GTPase proteins. Several of which have been confirmed with the bead-based AMPylation assays.
ContributorsGraves, Morgan C. (Author) / LaBaer, Joshua (Thesis director) / Qiu, Ji (Committee member) / Yu, Xiaobo (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor)
Created2013-05