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Myers-Irvin, Julie M. (2005) CHARACTERIZATION OF NUCLEAR MATRIX ALTERATIONS INVOLVED IN BLADDER CANCER PROGRESSION. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Bladder cancer, one of the most frequently diagnosed cancers, is a significant source of morbidity and mortality throughout the world. According to the American Cancer Society (2005), approximately 63,210 new cases will be diagnosed in the United States and bladder cancer will account for nearly 13,180 deaths. The current standard for detection of bladder cancer relies on cystoscopy, an invasive procedure, and cytology. Cytology has a high specificity, but lacks sensitivity in detection of low-grade tumors, as well as requires a trained pathologist for review. Because current diagnostic tools are less than optimal and because bladder cancer has a high rate of recurrence and long term monitoring is a necessity, a better diagnostic tool is needed. There is now a great interest in researching urine markers for bladder cancer. Our lab previously identified six nuclear structural proteins (BLCA 1-6) that are specifically expressed in bladder cancer tissue. The nuclear matrix is the support scaffold of the cell nucleus. This structure has a variety of functions, many of which have implications in cancer progression.The purpose of this dissertation is to examine changes in nuclear structural proteins. The hypothesis we propose is that changes in structural elements of the nucleus are involved in the progression of bladder cancer and can be developed into markers of this disease. Specifically this study had three goals. 1) to determine if BLCA-1 could be developed into a biomarker of bladder cancer, 2) to clone the gene encoding BLCA-1, and 3) to examine functional aspects of BLCA-4. A urine-based immunoassay was developed that can detect BLCA-1 in patients with bladder cancer with a specificity of 87% and sensitivity of 80%. Furthermore, this protein can be detected in serum of individuals with bladder cancer and may associate with the stage of disease. We also demonstrated that BLCA-4 can confer a growth advantage to cells over-expressing this protein. Over-expression of BLCA-4 led to many gene expression changes. BLCA-4 may play a role in bladder cancer pathobiology by altering genes that enhance proliferation and invasion, maintain blood flow for tumor cell survival, or enhance angiogenesis. Finally, we have been successful in cloning part of the cDNA that encodes for BLCA-1 and it appears to have a close homology to a novel metastasis related gene.In summary, this project has demonstrated that bladder cancer specific nuclear matrix proteins can be developed into markers of the disease and may play a functional role in bladder cancer pathobiology.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Myers-Irvin, Julie M.jmm30@pitt.eduJMM30
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairDeFranco, Dondod1@pitt.eduDOD1
Committee MemberPflug, Beth
Committee MemberBirder, Lori
Committee MemberYoshimura, Naoki
Committee MemberGetzenberg, Robert
Committee MemberGodfrey, Tony
Date: 25 July 2005
Date Type: Completion
Defense Date: 3 May 2005
Approval Date: 25 July 2005
Submission Date: 16 June 2005
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Institution: University of Pittsburgh
Schools and Programs: School of Medicine > Molecular Pharmacology
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: proteomics; tumor markers; Bladder cancer; nuclear matrix
Other ID:, etd-06162005-132736
Date Deposited: 10 Nov 2011 19:47
Last Modified: 15 Nov 2016 13:44


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