Matching Items (6)
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- All Subjects: Bexarotene
- Creators: School of Mathematical and Natural Sciences
- Resource Type: Text
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 effects that forensic-themed programs such as CSI: Crime Scene Investigation has on the public's understanding and expectations of the criminal justice system has been a main focus of study in recent years. This phenomenon was coined by the media and termed the "CSI Effect." This study aimed to research the correlations between age, gender, and program-watching habits on potential juries' evidence expectations in court. To do so, 70 people were surveyed and asked a series of demographic questions, as well as questions about how often they watch forensic-themed shows and their experience with the criminal justice system. They were given a mock crime scene scenario and asked about their scientific and non-scientific evidence expectations in this particular case. The most notable results showed that a longer exposure time to forensic-themed programs correlated to high evidence expectations. However, how often viewers watch forensic-themed programs did not seem to affect their evidence expectations. It was concluded that the higher evidence expectations by modern jurors may be due to a combination of the "CSI Effect" and the newly hypothesized "Tech Effect," instead of just being the consequence of the watching too much forensic-themed television.
ContributorsJones, Kristin Taylor (Author) / Kobojek, Kimberly (Thesis director) / Lafond, Sue (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Natural Sciences (Contributor)
Created2014-05
Description
Bexarotene (Bex) is a FDA-approved drug used to treat cutaneous T-cell lymphoma (CTCL). It binds with high affinity to the retinoid-X-receptor (RXR), a nuclear receptor implicated in numerous biological pathways. Bex may have the potential to attenuate estrogenic activity by acting as an estrogen receptor alpha (ERα) signaling antagonist, and can therefore be used to treat ERα-positive cancers, such as breast cancer. Using dual luciferase reporter assays, real-time qRT-PCR, and metabolic proliferation assays, the anti-estrogenic properties of Bex were ascertained. However, since Bex produces numerous contraindications, select novel RXR drug analogs were also evaluated. Results revealed that, in luciferase assays, Bex could significantly (P < 0.01) inhibit the transcriptional activity of ERα, so much so that it rivaled ER pan-antagonist ZK164015 in potency. Bex was also able to suppress the proliferation of two breast cancer cell models, MCF-7 and T-47D, and downregulate the expression of an estrogen receptor target gene (A-myb), which is responsible for cell proliferation. In addition, novel analogs A30, A33, A35, and A38 were evaluated as being more potent at inhibiting ERE-mediated transcription than Bex at lower concentrations. Analogs A34 and A35 were able to suppress MCF-7 cell proliferation to a degree comparable to that of Bex. Inhibition of T-47D cell proliferation, by contrast, was best achieved by analogs A34 and A36. For those with ERα – positive breast cancer who are refractory to current chemotherapeutics used to treat breast cancer, Bex and its analogs may prove to be useful alternative options.
ContributorsBains, Supreet (Author) / Jurutka, Peter (Thesis director) / Hackney Price, Jennifer (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
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
It is no surprise that crime has become an interest to people both nationally and globally. It is impossible to turn on a TV without hearing cable news talking about a bank robbery or a murder, or a political hearing of some sort. Crime TV shows are incredibly common—there are whole channels dedicated to just crime, and many prime-time TV shows deal with some form of crime, most often the law enforcement teams that interact with it. Movies and books about crime are also incredibly common—most movie theaters have at least one horror movie or psychological thriller on show at a given time, and books stores and libraries have entire sections about true crime and mysteries.
Crime has become an inescapable part of being a consumer and viewer in today’s society. The interest in crime, however, could not have just been created by the media or a few specific parties and gained the amount of attention that is has today. Crime has been of interest since ancient times, seen immortalized in art and literature with famous events like the death of Socrates and the assassination of Julius Caesar. However, only more modern advances in media and the growth in consumerism could have led to interest and commodification of crime as we see it today. Landmark cases like Ted Bundy and O.J. Simpson have contributed to the growth of the media landscape, but because of the cyclical nature of the news and consumer cycle, these cases would not differ much in the way that they would be covered today, even with the new methods of disseminating information that we have today, such as social media and news websites that are accessible by everyone. Crime as entertainment has been a product not just of the media and popular culture but also from American consumers who continue to give media and pop culture producers a consumer who wishes to view their content and to continue to further the interest in crime. Media and popular culture are not the only people to blame for the popularization of crime as a product; people in the United States, and globally, are just as much responsible for the creation of crime as entertainment.
Crime has become an inescapable part of being a consumer and viewer in today’s society. The interest in crime, however, could not have just been created by the media or a few specific parties and gained the amount of attention that is has today. Crime has been of interest since ancient times, seen immortalized in art and literature with famous events like the death of Socrates and the assassination of Julius Caesar. However, only more modern advances in media and the growth in consumerism could have led to interest and commodification of crime as we see it today. Landmark cases like Ted Bundy and O.J. Simpson have contributed to the growth of the media landscape, but because of the cyclical nature of the news and consumer cycle, these cases would not differ much in the way that they would be covered today, even with the new methods of disseminating information that we have today, such as social media and news websites that are accessible by everyone. Crime as entertainment has been a product not just of the media and popular culture but also from American consumers who continue to give media and pop culture producers a consumer who wishes to view their content and to continue to further the interest in crime. Media and popular culture are not the only people to blame for the popularization of crime as a product; people in the United States, and globally, are just as much responsible for the creation of crime as entertainment.
ContributorsCooke, Emilie (Author) / Kobojek, Kimberly (Thesis director) / Gordon, Karen (Committee member) / School of Criminology and Criminal Justice (Contributor) / School of Mathematical and Natural Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05