Browsing by Subject "ovarian cancer"
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Item Development of a Biomarker Profile for Ovarian Cancer Using Proseek® Multiplex Plates(2016-05)Ovarian cancer is the fifth leading cause of cancer death in women in the U.S. Currently, two serum biomarkers, CA125 and HE4, are used to monitor recurrence of ovarian cancer. However, their specificity and sensitivity are not adequate for detecting early stages of ovarian cancer in the general population. In this project, we used a multiplex approach to identify new candidate biomarkers for early stages of ovarian cancer. We used a Proseek® Multiplex Oncology plate (Olink Bioscience) to analyze the expression of 92 biomarkers in 1 µL of serum collected from 22 women in each of four groups: healthy, benign ovarian tumors, early stage ovarian cancer, and late stage ovarian cancer. Biomarker levels were analyzed by a Proximity Extension Assay and quantitative real-time polymerase chain reaction. As expected, CA125 and HE4 showed the highest variation between healthy versus early stage ovarian cancer (AUC=0.981 and 0.844, respectively). Interestingly, 18 additional proteins were identified as potential candidate biomarkers with AUC > 0.70. To validate these results, we plan to test hundreds of serum samples on Proseek® plates. Our ultimate goal is to develop an algorithm of biomarkers that can be used to screen women for early stages of ovarian cancer, when the likelihood of long term survival is greatest.Item Development of giant magnetoresistive biosensors and systems for early disease detection(2018-02) Klein, ToddGiant magnetoresistance (GMR) biosensors have been used with great success for the detection of a variety of biomarkers. Linear GMR biosensors were first proposed in 1998 and have been used since then. The major scientific contribution of this dissertation is to go beyond the previously published models for the linear GMR biosensor and provide analysis of practical design decisions that occur during sensor fabrication. I highlight the central role played by GMR free layer stray field near the sensor edge and present a numerical calculation to guide future linear GMR biosensor design. In addition, I explain how I proposed and demonstrated a novel, non-linear, domain-wall based GMR biosensor, in an effort to detect single molecules. I also describe my contributions to an effort to understand and build upon a previous experimental result using a large area sensor with multidomain switching. The major technological contribution described in this dissertation is the development of a GMR biosensing system that can potentially contribute to the early detection of ovarian cancer and serve as a platform for detecting a wide variety of other biomarkers. System integration included spintronic and nanomagnetic materials engineering, design of a coil with a ferrite core, electrical engineering, analog and digital signal processing, firmware programming, user interface programming on both a PC and an Android smartphone, communications over both USB and Bluetooth, and mechanical design. Hand-held and bench-top systems of this GMR bionsensor were both developed. Both versions use the same sensors, electrical hardware, firmware, and software, but differ mechanically and in the number of sensors available per assay. The bench-top version was completed first and used to demonstrate high sensitivity multiplex detection of ovarian cancer biomarkers CA-125, HE-4, and IL-6, with limits of detection below 10 pg/mL. The hand-held version was then completed and used with a preliminary biotin-streptavidin demonstration. Further development of the hand-held system involves integrating microfluidics.Item Ovarian cancer screening in high risk individuals..(2009-05-04) Dvorak, LeahCurrently, 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.Item tRNA Fragments: Expression and Function in Ovarian Cancer(2017-09) Zhou, KunDeep sequencing studies of noncoding RNA in liquid biopsies are revealing a vast repertoire of potential biomarkers. Ovarian cancer is a difficult-to-diagnose disease, urgently requiring novel and readily accessible biomarkers. We hypothesized that urine, one source of liquid biopsy samples, may contain novel noncoding RNAs (ncRNAs) that could serve as biomarkers for ovarian cancer. We proceeded to deep sequence RNA extracted from urine collected from ovarian cancer patients to better understand the repertoire of small RNAs in this type of liquid biopsy sample. The ncRNAs identified in these urine samples were predominantly microRNAs (miRNAs), ribosomal RNA (rRNA) fragments and tRNA fragments (tRFs). tRFs are a group of ncRNAs, which have been found across the biological kingdom and are increasingly being studied for their role in cancer biology. Several tRFs have been studied in cancer, although not previously in ovarian cancer. We have studied the expression of one specific tRF, 5’ fragment of tRNA-Glu-CTC (tRF5-Glu), in five different ovarian cancer cell lines. Several variants of tRF5-Glu were identified and we have now confirmed the expression of tRF5-Glu in ovarian cancer cells by quantitative real-time PCR (qRT-PCR), Northern analysis and ligation PCR. Additionally, we determined that angiogenin (ANG) plays a role in the biogenesis of tRF5-Glu. Furthermore, we have shown that tRF5-Glu targets the mRNA of the Breast Cancer Anti-estrogen Resistance 3 (BCAR3). While BCAR3 is known to regulate cancer cell migration and contributes to anti-estrogen resistance in breast cancer cells, it has not previously been studied in ovarian cancer or shown to be targeted by a tRF. Using synthetic mimics of tRF5-Glu and siRNAs targeting BCAR3, we were able to show that tRF5-Glu expression and the knock down of BCAR3 expression inhibits proliferation in ovarian cancer cells. These studies demonstrate that tRF5-Glu contributes to the regulation of BCAR3 and provides a novel mechanism of the regulation of proliferation in ovarian cancer cell lines.