Matching Items (5)
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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

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 (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

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
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Description

Telomeres are structures at the ends of DNA strands that get longer in the DNA of sperm cells as males age. That phenomenon is different for most other types of cells, for which telomeres get shorter as organisms age. In 1992, scientists showed that telomere length (TL) in sperm increases

Telomeres are structures at the ends of DNA strands that get longer in the DNA of sperm cells as males age. That phenomenon is different for most other types of cells, for which telomeres get shorter as organisms age. In 1992, scientists showed that telomere length (TL) in sperm increases with age in contrast to most cell of most other types. Telomeres are the protective caps at the end of DNA strands that preserve chromosomal integrity and contribute to DNA length and stability. In most cells, telomeres shorten with each cell division due to incomplete replication, though the enzyme telomerase functions in some cell lines that undergo repetitive divisions to replenish any lost length and to prevent degradation. Cells, and therefore organisms, with short telomeres are more susceptible to mutations and genetic diseases. While TL increases in a subset of sperm cells and longer telomeres may prevent early disintegration of DNA, it may also prevent natural mechanisms of apoptosis, or cell death, from occurring in abnormal sperm.

Created2017-02-07
Description

Thalidomide is a sedative drug introduced to European markets on 1 October 1957 after extensive testing on rodent embryos to ensure its safety. Early laboratory tests in rodent populations showed that pregnant rodents could safely use it, so doctors prescribed Thalidomide to treat morning sickness in pregnant women. However, in

Thalidomide is a sedative drug introduced to European markets on 1 October 1957 after extensive testing on rodent embryos to ensure its safety. Early laboratory tests in rodent populations showed that pregnant rodents could safely use it, so doctors prescribed Thalidomide to treat morning sickness in pregnant women. However, in humans Thalidomide interfered with embryonic and fetal development in ways not observed in rodent tests. Pregnant women who take Thalidomide are at grater than normal risk for spontaneous abortion and for giving birth to children with developmental anomalies such as shortened, absent, or extra limbs, as well as a variety of heart, ear, and internal organ defects. The failure of rodent models to inform scientists of Thalidomide's teratogenicity in humans ignited debate about the proper use of cross-species testing during drug development.

Created2014-03-07
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Description

Aristotle studied developing organisms, among other things, in ancient Greece, and his writings shaped Western philosophy and natural science for greater than two thousand years. He spent much of his life in Greece and studied with Plato at Plato's Academy in Athens, where he later established his own school called

Aristotle studied developing organisms, among other things, in ancient Greece, and his writings shaped Western philosophy and natural science for greater than two thousand years. He spent much of his life in Greece and studied with Plato at Plato's Academy in Athens, where he later established his own school called the Lyceum. Aristotle wrote greater than 150 treatises on subjects ranging from aesthetics, politics, ethics, and natural philosophy, which include physics and biology. Less than fifty of Aristotle's treatises persisted into the twenty-first century. In natural philosophy, later called natural science, Aristotle established methods for investigation and reasoning and provided a theory on how embryos generate and develop. He originated the theory that an organism develops gradually from undifferentiated material, later called epigenesis.

Created2016-07-07