Matching Items (4)
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- All Subjects: Bexarotene
- All Subjects: Lyme disease
- Creators: Hackney Price, Jennifer
- Creators: Knochel, Amanda Marie
- Member of: Barrett, The Honors College Thesis/Creative Project Collection
- Member of: Theses and Dissertations
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
This past summer, I met a young lady named Ashley (name has been changed) who has been diagnosed with chronic Lyme disease. Upon researching this condition in greater detail, I learned that many medical providers who base their practice on the best evidence do not support treating patients for a chronic Lyme infection, the existence of which has not been substantially supported with research. I inquired about the process that led her to seek treatment for chronic Lyme disease at Jemsek Specialty Clinic. I learned that after many inaccurate diagnoses and years of unhelpful treatments, Ashley finally rejected the help offered by traditional medical doctors because she felt they were uncaring and inattentive, and went somewhere she felt heard. What she deserved, however, was both care that was based in scientific research and care that felt compassionate, as has been promoted by the nursing field. Despite the lack of a confirmed medical diagnosis, Ashley's day to day symptoms and struggles could be addressed with nursing care. I then constructed a nursing care plan to be implemented by Ashley's family and friends to help her feel her best and live a fulfilling life despite chronic disease. Patients should not have to choose between a healthcare provider who utilizes the strongest scientific evidence and one they feel understands them, though many do. Nursing can unite these mindsets by alleviating the daily challenges patients face. Please see the website http://careplanforashley.blogspot.com
ContributorsKnochel, Amanda Marie (Author) / Panchmatia, Bella (Thesis director) / Mishark, Kenneth (Committee member) / Barrett, The Honors College (Contributor) / Arizona State University. College of Nursing & Healthcare Innovation (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
A long personal struggle with Lyme disease prompted me to review the current literature to better understand what remains elusive to researchers and physicians. Lyme disease was first discovered in Connecticut in the mid-1970’s, however, in Europe, it was already being treated with antibiotics. The disease is caused by a spirochete bacteria named Borrelia burgdorferi after the scientist who married the European syndromes associated with the microbe to the disease found in the United States. Borrelia burgdorferi is capable of evading the immune system through a variety of methods, some of which are still not clearly understood. Treatment for Lyme disease is effective and involves antibiotics over a variable duration depending on the presentation of the disease. Post-treatment Lyme Disease Syndrome (PTLDS) is the heart of the controversy surrounding this disease as patients continue to have debilitating symptoms with no clear cause.
ContributorsBailey, Susan Caroline (Author) / Hackney Price, Jennifer (Thesis director) / Marshall, Pamela (Committee member) / School of Mathematical and Natural Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05