Browsing by Subject "screening"

Now showing 1 - 8 of 8
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    Biochemical and Biophysical Assay Development for Screening and Characterization of Small Molecules and Synthesized Analogues Targeting Human Cytosine Deaminases
    (2023-01) Grillo, Michael
    The APOBEC3 family of enzymes converts cytosine to uracil in single-stranded DNA as a part of the innate immune defense against viruses. A large body of work has demonstrated that when dysregulated, APOBEC3s contribute to mutagenesis of somatic DNA in cancer. These mutational events lead to poor clinical outcomes such as tumor recurrence, metastasis, and therapeutic resistance. Because of this, we are interested in targeting APOBEC3s for inhibition by small molecules with the goal of improving the outcome of treatment with current cancer therapies. Chapter 1 introduces APOBEC3s as targets of interest with commentary on current and potential biochemical, biophysical, cellular, and in vivo assay technologies to evaluate potential inhibitors. Chapter 2 discusses careful in silico reconstruction of APOBEC3B followed by molecular dynamics simulations and druggability analysis identifying putative allosteric sites. Virtual screening was performed, and compounds were validated in biochemical and biophysical assays to serve as potential starting points for hit to lead optimization. Chapter 3 focuses on the development of sensitive biophysical assays and implementation in fragment screening. One fragment was validated during triage and served as a starting point for preliminary structure-activity relationship studies on two potentially divergent chemical series. Chapter 4 discusses the development of a real-time fluorescence-based activity assay for human cytidine deaminase utilizing a fluorogenic substrate. This assay was validated with known small molecule inhibitors and implemented in a fragment screen to discover novel non-nucleoside inhibitors of cytidine deaminase. The long-term goal of this work is to apply the same technology to measure APOBEC3 activity. Chapter 5 outlines several attempts at synthesizing a rationally designed covalent sulfur (VI) fluoride exchange probe targeting conserved hydroxyl-containing residues in the APOBEC3 active site. A variety of standard, as well as novel, approaches to nucleoside chemistry were explored with the goal of eventually incorporating a covalent warhead into a DNA oligonucleotide. Finally, Appendix A describes attempts at expressing and purifying A3B containing 5-fluorotryptophan as a tool for protein-observed 19F-NMR experiments.
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    Breast Cancer Screening: What you need to know as an informed patient
    (2008-09-02) Prebil, Sarah
    Currently, self breast exams as well as clinical breast exams are viewed as possibly cost-saving and life-saving practices for women around the world. However, given the analysis of two large scale studies, self-breast exams accomplish neither of these goals. In fact, these breast exams may be causing more harm than no intervention at all because of unnecessary breast biopsies. Therefore, regular self breast examination cannot be recommended. For screening, women should be aware of any changes in their breasts and see a doctor if a change occurs. Starting at age 40, women should get yearly mammograms.
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    Colon Cancer Screening: What you should know
    (2009-05-06) Abdihalim, Mohamed
    The less invasive nature of CT colonography and low risk of procedure related complications as compared to colonoscopy may be attractive to patients and may improve screening adherence. In screening asymptomatic patients with average risk for colorectal cancer, CT colonography has been shown to have high sensitivity when optical colonoscopy is used as the reference standard.
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    The fecal immunochemical test (FIT) has high sensitivity and specificity in screening for colon cancer.
    (2010-07-29) Knutson, Marit
    Newer stool tests (fecal immunochemical test) may be better than the usual stool test (guaiac) for detecting colon cancer. The FIT might be more useful than the current guaiac test for colon cancer screening.
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    Geriatric Health Care Maintenance
    (2008-12-02) Loritz, Sara
    A checklist of key screening tests persons over age 65 should be asking their physicians about. These include tests for everyone (ie. colonscopy) as well as tests for women (ie. mammography) and men (ie. PSA blood test).
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    Ovarian cancer screening in high risk individuals..
    (2009-05-04) Dvorak, Leah
    Currently, there is no good screening test for ovarian cancer. The screening tests used are more useful in women who are at high risk of developing ovarian cancer, but they are far from perfect. Whether these screening tests will reduce the number of women who die from ovarian cancer remains to be seen with the completion of the Prostate, Lung, Colon, and Ovarian cancer trial. The results from this trial are projected to be available in 2016.
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    Pancreatic cancer screening: information for high-risk patients
    (2008-09-02) Scott, Matthew
    Although risk stratification of patients with a family history of pancreatic cancer is difficult, screening by endoscopic ultrasound (EUS) is cost effective and increases life expectancy in those people at high risk.
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    Pregnancy After Age 35
    (2010-07-29) Roberts, Kara S.
    Screening for possible aneuploidies, especially trisomy 21 or Down Syndrome, is generally offered to all women early in their pregnancy. The question is when that screening should be done to provide the most reliable and useful information. This article showed that combined serum (pregnancy associated plasma protein A and free beta subunit of human chorionic gonadotropin) and ultrasound testing (looking for nuchal translucency) early in their first trimester in addition to serum testing (quad screen) in their second trimester provided the most reliable results.