Matching Items (143)
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
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
G3Box's 2013 Marketing Plan outlines a strategic plan and short term operational strategies for the company. The document includes a discussion of the company's decision to enter the market for healthcare facilities in developing counties, and a situation assessment of the market conditions. G3Box is targeting small and large NGOs that currently provide healthcare facilities in developing countries. The market size for healthcare aid in developing countries is estimated to be $1.7 billion. The plan also analyses the customer's value chain and buying cycle by using voice of the customer data. The strategic position analysis profiles G3Box's competition and discusses the company's differential advantage versus other options for healthcare facilities in developing countries. Next the document discusses G3Box's market strategy and implementation, along with outlining a value proposition for the company. G3Box has two objectives for 2013: 1) Increase sales revenue to $1.3 million and 2) increase market presence to 25%. In order to reach these objectives, G3Box has developed a primary and secondary strategic focus for each objective. The primary strategies are relationship selling and online marketing. The secondary strategies are developing additional value-added activities and public relations.
ContributorsWalters, John (Author) / Denning, Michael (Thesis director) / Ostrom, Lonnie (Committee member) / Carroll, James (Committee member) / Barrett, The Honors College (Contributor) / Ira A. Fulton School of Engineering (Contributor)
Created2012-12
Description
The majority of the 52 photovoltaic installations at ASU are governed by power purchase agreements (PPA) that set a fixed per kilowatt-hour rate at which ASU buys power from the system owner over the period of 15-20 years. PPAs require accurate predictions of the system output to determine the financial viability of the system installations as well as the purchase price. The research was conducted using PPAs and historical solar power production data from the ASU's Energy Information System (EIS). The results indicate that most PPAs slightly underestimate the annual energy yield. However, the modeled power output from PVsyst indicates that higher energy outputs are possible with better system monitoring.
ContributorsVulic, Natasa (Author) / Bowden, Stuart (Thesis director) / Bryan, Harvey (Committee member) / Sharma, Vivek (Committee member) / Barrett, The Honors College (Contributor) / School of Sustainability (Contributor) / Ira A. Fulton School of Engineering (Contributor)
Created2012-12
Description
The 21st century engineer will face a diverse set of challenges spread out along a broad spectrum of disciplines. Among others, the fields of energy, healthcare, cyberspace, virtual reality, and neuroscience require monumental efforts by the new generation of engineers to meet the demands of a growing society. However the most important, and likely the most under recognized, challenge lies in developing advanced personalized learning. It is the core foundation from which the rest of the challenges can be accomplished. Without an effective method of teaching engineering students how to realize these grand challenges, the knowledge pool from which to draw new innovations and discoveries will be greatly diminished. This paper introduces the Inventors Workshop (IW), a hands-on, passion-based approach to personalized learning. It is intended to serve as a manual that will inform the next generation of student leaders and inventioneers about the core concepts the Inventors Workshop was built upon, and how to continue improvement into the future. Due to the inherent complexities in the grand challenge of personalized learning, the IW has developed a multifaceted solution that is difficult to explain in a single phrase. To enable comprehension of the IW's full vision, the process undergone to date of establishing and expanding the IW is described. In addition, research has been conducted to determine a variety of paths the Inventors Workshop may utilize in future expansion. Each of these options is explored and related to the core foundations of the IW to assist future leaders and partners in effectively improving personalized learning at ASU and beyond.
ContributorsEngelhoven, V. Logan (Author) / Burleson, Winslow (Thesis director) / Peck, Sidnee (Committee member) / Fortun, A. L. Cecil (Committee member) / Barrett, The Honors College (Contributor) / Ira A. Fulton School of Engineering (Contributor)
Created2012-12
ContributorsShah, Beejal (Author) / Nakamura, Mutsumi (Thesis director) / Balasooriya, Janaka (Committee member) / Wilkerson, Kelly (Committee member) / Ira A. Fulton School of Engineering (Contributor) / Barrett, The Honors College (Contributor)
Created2012-12
Description
The Phoenix-Metro area currently has problems with its transportation systems. Over-crowded and congested freeways have slowed travel times within the area. Express bus transportation and the existence of "High Occupancy" lanes have failed to solve the congestion problem. The light rail system is limited to those within a certain distance from the line, and even the light rail is either too slow or too infrequent for a commuter to utilize it effectively. To add to the issue, Phoenix is continuing to expand outward instead of increasing population density within the city, therefore increasing the time it takes to travel to downtown Phoenix, which is the center of economic activity. The people of Phoenix and its surrounding areas are finding that driving themselves to work is just as cost-effective and less time consuming than taking public transportation. Phoenix needs a cost-effective solution to work in co- existence with improvements in local public transportation that will allow citizens to travel to their destination in just as much time, or less time, than travelling by personal vehicle.
ContributorsSerfilippi, Jon (Author) / Ariaratnam, Samuel (Thesis director) / Pendyala, Ram (Committee member) / Pembroke, Jim (Committee member) / Barrett, The Honors College (Contributor) / Ira A. Fulton School of Engineering (Contributor)
Created2012-12
Description
Electrospun nanofibers can be prepared from various kinds of inorganic substances by electro-spinning techniques. They have great potential in many applications including super capacitors, lithium ion batteries, filtration, catalyst and enzyme carriers, and sensors [1]. The traditional way to produce electrospun nanofibers is needle based electro-spinning [1]. However, electrospun nanofibers have not been widely used in practice because of low nanofiber production rates. One way to largely increase the electro-spinning productivity is needleless electro-spinning. In 2005, Jirsak et al. patented a rotating roller fiber generator for the mass production of nanofibers [2]. Elmarco Corporation commercialized this technique to manufacture nanofiber equipment for the production of all sorts of organic and inorganic nanofibers, and named it "NanospiderTM". For this project, my goal is to build a needleless electro-spinner to produce nanofibers as the separator of lithium ion batteries. The model of this project is based on the design of rotating roller fiber generator, and is adapted from a project at North Dakota State University in 2011 [3].
ContributorsQiao, Guanhao (Author) / Yu, Hongyu (Thesis director) / Jiang, Hanqing (Committee member) / Goryll, Michael (Committee member) / Barrett, The Honors College (Contributor) / Ira A. Fulton School of Engineering (Contributor)
Created2012-12
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