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- All Subjects: Bexarotene
- Creators: Marshall, Pamela
- Member of: Barrett, The Honors College Thesis/Creative Project Collection
- Status: Published
Description
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
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 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
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 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
Description
Rheumatoid Arthritis (RA) is an autoimmune disorder where the body mistakenly attacks healthy joints. This in turn causes inflammation resulting in pain and swelling. It is very important to get RA accurately diagnosed and treated as early as possible. Similarly, with any disease: the longer it is left untreated, the more damage it can cause. RA can cause irreversible joint damage leading to disability. The purpose of this study is to determine if oral microbiome can be used as an additional criterion to aid in diagnosing RA. Several oral microbes have already been identified as biomarkers for RA in saliva. In this study, 10 participants were recruited: 6 diagnosed with RA and 4 Healthy as a control. Two subgroups of RA were done within this study; those diagnose with a positive Rheumatoid Factor (RF) and those diagnose with a negative RF. These subgroups were then compared in order to determine the validity of using certain microbes as biomarkers for RA even when different diagnostic criteria were met. The microbe Parahaemolyticus had the largest measure of effect, showing the greatest potential for statistically significant results with a larger sample size. If we can work narrow to down specific microbes to be undoubtedly higher in abundance with already diagnosed RA patients when comparing to healthy participants, this will be a gamechanger. Not only could we give a higher sense of confidence with the diagnosis of RA, but this could streamline RA diagnosis.
ContributorsNunez, Celeste (Author) / Marshall, Pamela (Thesis director) / Hackney Price, Jennifer (Committee member) / Kizer, Elizabeth (Committee member) / College of Health Solutions (Contributor) / Barrett, The Honors College (Contributor)
Created2020-12