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Bexarotene is a commercially produced drug commonly known as Targetin presecribed to treat cutaneous T-cell lymphoma (CTCL). Bex mimics the actions of natural 9-cis retinoic acid in the body, which are derived from Vitamin A in the diet and boost the immune system. Bex has been shown to be effective

Bexarotene is a commercially produced drug commonly known as Targetin presecribed to treat cutaneous T-cell lymphoma (CTCL). Bex mimics the actions of natural 9-cis retinoic acid in the body, which are derived from Vitamin A in the diet and boost the immune system. Bex has been shown to be effective in the treatment of multiple types of cancer, including lung cancer. However, the disadvantages of using Bex include increased instances of hypothyroidism and excessive concentrations of blood triglycerides. If an analog of Bex can be developed which retains high affinity RXR binding similar to the 9-cis retinoic acid while exhibiting less interference for heterodimerization pathways, it would be of great clinical significance in improving the quality of life for patients with CTCL. This thesis will detail the biological profiling of additional novel (Generation Two) analogs, which are currently in submission for publication, as well as that of Generation Three analogs. The results from these studies reveal that specific alterations in the core structure of the Bex "parent" compound structure can have dramatic effects in modifying the biological activity of RXR agonists.
ContributorsYang, Joanna (Author) / Jurutka, Peter (Thesis director) / Wagner, Carl (Committee member) / Hibler, Elizabeth (Committee member) / Barrett, The Honors College (Contributor)
Created2012-05
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Description
Bexarotene (Targretin®) is an FDA approved drug used to treat cutaneous T-cell lymphoma (CTCL), as well as off-label treatments for various cancers and neurodegenerative diseases. Previous research has indicated that bexarotene has a specific affinity for retinoid X receptors (RXR), which allows bexarotene to act as a ligand-activated-transcription factor

Bexarotene (Targretin®) is an FDA approved drug used to treat cutaneous T-cell lymphoma (CTCL), as well as off-label treatments for various cancers and neurodegenerative diseases. Previous research has indicated that bexarotene has a specific affinity for retinoid X receptors (RXR), which allows bexarotene to act as a ligand-activated-transcription factor and in return control cell differentiation and proliferation. Bexarotene targets RXR homodimerization to drive transcription of tumor suppressing genes; however, adverse reactions occur simultaneously when bound to other nuclear receptors. In this study, we used novel bexarotene analogs throughout 5 iterations synthesized in the laboratory of Dr. Wagner to test for their potency and ability to bind RXR. The aim of our study is to quantitatively measure RXR homodimerization driven by bexarotene analogs using a yeast two-hybrid system. Our results suggests there to be several compounds with higher protein activity than bexarotene, particularly in generations 3.0 and 5.0. This higher affinity for RXR homodimers may help scientists identify a compound that will minimize adverse effects and toxicity of bexarotene and serve as a better cancer treatment alternative.
ContributorsSeto, David Hua (Author) / Marshall, Pamela (Thesis director) / Wagner, Carl (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Natural Sciences (Contributor) / School of Social and Behavioral Sciences (Contributor)
Created2015-05
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Description

In 2018, the United States generated 37.4 million more U.S. tons of paper and cardboard material compared to in 1960 (EPA, 2020). As the United States produces a disproportionate amount of packaging waste every year when accounting for population size, it has become increasingly difficult to mitigate waste production, lessen

In 2018, the United States generated 37.4 million more U.S. tons of paper and cardboard material compared to in 1960 (EPA, 2020). As the United States produces a disproportionate amount of packaging waste every year when accounting for population size, it has become increasingly difficult to mitigate waste production, lessen the environmental impact of generating more paperboard materials, and move towards a more ethical circular economy. In efforts to adopt the principles of a green economy, deviate from the linear supply chain model, minimize packaging waste, and encourage more sustainable lifestyles, we developed a business centered around a circular, service based model called Room & Cardboard. Our initiative collects cardboard waste generated in and around the ASU community and repurposes it for dorm-style furniture available for students to rent throughout the school year. Using cardboard, we have built prototypes for two products (desk lamps and shoe racks) that are sturdy, visually pleasing, and recyclable. Our initiative helps to reduce cardboard packaging waste by upcycling cardboard waste into products that will increase the lifespan of the cardboard material. At the end of the product’s life span, in cases of severe damage, we will turn the product into a seed board made with blended cardboard paste that can then be used to plant a succulent we will make available to students to buy as dorm decor. The feedback on our initiative through online surveys and in-person tabling has generated enough traction for Dean Rendell of Barrett, the Honors College at Arizona State University to consider a test-drive of our products in the upcoming Fall semester.

ContributorsIslam, Shauda (Co-author) / Norvell, Macey (Co-author) / Werner, Isabella (Co-author) / Byrne, Jared (Thesis director) / Marseille, Alicia (Committee member) / Jordan, Amanda (Committee member) / School of Mathematical and Natural Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Description

Collective human attitudes influenced by macro-forces that impact environmental issues are partially correlated to our behaviors for the good and the harm of the planet. In this thesis, I will explore how collective human attitudes contribute to pro-environmental behaviors, common and pre-existing frames of mind on major conservation dilemmas, and

Collective human attitudes influenced by macro-forces that impact environmental issues are partially correlated to our behaviors for the good and the harm of the planet. In this thesis, I will explore how collective human attitudes contribute to pro-environmental behaviors, common and pre-existing frames of mind on major conservation dilemmas, and finally suggest future directions on how humans could be inclined to take on more environmental responsibility through an increase in human-environmental connectivity. It is found that humans are largely driven by institution structures, education, and social influence. In conclusion, more efforts should be placed to further analyze these structural incentives for pro-environmental behaviors and use them to make environmental stewardship more accessible for all people and diverse circumstances. This can be done by evaluating the human dimensions of what influences human attitudes and behaviors, how to use these forces to systematically influence pro-environmental choices, applying these structural forces to main conservation issues, and further incorporating moral discourse into the environmental research in order to appeal correctly to all aspects and perspectives. Only when human connectivity is understood in relation to the natural sciences will we be able to make positive change in the direction of a healthier Earth.

ContributorsCheek, Alana C (Author) / Vargas, Perla (Thesis director) / Keahey, Jennifer (Committee member) / School of Humanities, Arts, and Cultural Studies (Contributor) / School of Mathematical and Natural Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description

The ever-increasing importance of cancer and neurodegenerative diseases continues to grow as populations across the world are affected by death and aging. The vitamin A (RXR) and vitamin D (VDR) receptor pathways offer promising potential to aid in treatment of cancer and Alzheimer’s disease. This thesis discusses the potential application

The ever-increasing importance of cancer and neurodegenerative diseases continues to grow as populations across the world are affected by death and aging. The vitamin A (RXR) and vitamin D (VDR) receptor pathways offer promising potential to aid in treatment of cancer and Alzheimer’s disease. This thesis discusses the potential application of novel analogs of Bexarotene (RXR agonist), MeTC7 (a new potent VDR antagonist), and vitamin D as possible therapeutics for cancer and Alzheimer’s disease.

ContributorsHong, Jennifer (Author) / Jurutka, Peter (Thesis director) / Wagner, Carl (Committee member) / Marshall, Pamela (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Natural Sciences (Contributor)
Created2023-05