Zhilian Wang

Abstract

Telomerase is a ribonucleoprotein enzyme that is able to add telomeric repeats to the ends of eukaryotic DNA to stabilize chromosomes. Telomerase is active in germline cells, stem cells and tumor cells, but not in most human somatic cells. In this study we report the extended use of the Telomeric Repeat Amplification Protocol (TRAP) assay for the detection of telomerase activity in prostate needle biopsy specimens and freshly collected prostatic fluid. Clinical application of a newly developed PCR-ELISA telomerase assay method is also evaluated. Multiple sextant needle biopsy specimens from 56 subjects and prostatic secretion specimens from 72 subjects, with or without prostate cancer (PCa), were examined. In the needle core group the test results showed 90% sensitivity and 78% specificity for the detection of prostate cancer. In the prostatic secretion group the sensitivity was 77% and the specificity 84%. Statistical analysis of both groups revealed that higher positive rates and stronger telomerase activity were associated with higher Gleason scores and tumor anaplasia. The data from a comparison of telomerase activity with volume of cancer in the needle cores demonstrated that greater telomerase activity was always coupled with higher cancer volume. We also demonstrated a high correlation between telomerase activity in prostatic secretion specimens and serum PSA values. In a comparison study, we tested telomerase activity in 48 prostate needle cores containing or not containing cancer cells, and in 18 prostatic fluid specimens from patients with or without PCa by both the PCR-ELIS A method and the TRAP assay. The assay results showed high correlation between two methods.

In conclusion, telomerase activity was reliably detected by each method in specimens of both types. It may be clinically meaningful to apply this new assay system for determining telomerase activity because by its sensitivity it provides valuable information for early diagnosis, and beyond that for therapeutic evaluation of prostate cancer patients.

LLU Discipline

Biochemistry

Department

Biochemistry

School

Graduate School

First Advisor

Richard E. Beltz

Second Advisor

E. Clifford Herrmann

Third Advisor

William H. R. Langridge

Fourth Advisor

Herbert C. Ruckle

Fifth Advisor

Charles W. Slattery

Degree Name

Doctor of Philosophy (PhD)

Degree Level

Ph.D.

Year Degree Awarded

2000

Date (Title Page)

6-2000

Language

English

Library of Congress/MESH Subject Headings

Prostatic Neoplasms -- diagnosis; Telomerase -- antagonists and inhibitors; RNA-Directed DNA Polymerase; Prostate -- cytology

Type

Dissertation

Page Count

xv; 151

Digital Format

PDF

Digital Publisher

Loma Linda University Libraries

Usage Rights

This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights.

Collection

Loma Linda University Electronic Theses and Dissertations

Collection Website

http://scholarsrepository.llu.edu/etd/

Repository

Loma Linda University. Del E. Webb Memorial Library. University Archives

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