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Circulating Biomarkers in the Study and Early Detection of Ovarian Cancer

Nolen, Brian Michael (2011) Circulating Biomarkers in the Study and Early Detection of Ovarian Cancer. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Abstract

Ovarian cancer, the most lethal of all gynecological malignancies, represents a significant public health burden to women worldwide. The current challenges associated with ovarian cancer stem from a lack of effective screening strategies, an inability to detect the disease at a treatable stage, and the disappointing impact of treatment regimens over the entire disease course. A multi-faceted evaluation of circulating biomarkers of ovarian cancer was conducted in order to identify specific biomarkers and combinations which might serve as effective tools in the screening, triage, and therapeutic targeting of ovarian cancer patients. Ovarian epithelial carcinoma (OEC) represents a heterogeneous disease characterized by several histological subtypes displaying divergent etiology, pathology, and treatment responsiveness. Serum biomarkers were identified which displayed subtype-specific alterations in a comparison of OEC patients and benign controls. These results suggest that circulating biomarkers may assist in the selection of patients for targeted therapies. The efficient triage of women diagnosed with a pelvic mass based on risk of malignancy is known to result in a significant improvement in outcome for ovarian cancer patients and also a significant reduction in morbidity and anxiety for women with benign masses. Several multimarker panels, including the optimal combination of CA 125 and HE4, were capable of discriminating benign from malignant pelvic masses. Based on current and previous findings, this biomarker panel may represent a novel diagnostic tool in this clinical setting. Urine may offer several distinct advantages over serum as an analytical biofluid based on its low complexity, high stability, and lack of invasivity. An analysis of urine biomarkers revealed that several previously identified ovarian cancer biomarkers offer higher diagnostic performance in urine versus serum. Urine multimarker panels were effective in discriminating ovarian cancer cases from controls while a combination of urine and serum biomarkers resulted in the highest performance. The current study provides compelling evidence for the use of circulating biomarkers in several capacities within the setting of ovarian cancer. The collective impact of biomarker research on the clinical management of ovarian cancer has the potential to significantly improve overall public health.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Nolen, Brian Michaelnolanb@upmc.edu
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairLokshin, Anna E.lokshina@upmc.edu
Committee MemberFeingold , Eleanorfeingold@pitt.eduFEINGOLD
Committee MemberLinkov, Faina L.faina.linkov@gmail.com
Committee MemberBarmada, M. Michaelbarmada@pitt.eduBARMADA
Committee MemberKalinski, Pawelkalinskip@upmc.eduPAK5
Date: 22 September 2011
Date Type: Completion
Defense Date: 3 May 2011
Approval Date: 22 September 2011
Submission Date: 20 May 2011
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Human Genetics
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: biomarkers; early detection; screening; ovarian cancer; pelvic mass
Other ID: http://etd.library.pitt.edu/ETD/available/etd-05202011-144012/, etd-05202011-144012
Date Deposited: 10 Nov 2011 19:45
Last Modified: 19 Dec 2016 14:36
URI: http://d-scholarship.pitt.edu/id/eprint/7928

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